Pharmaceutical and cosmetic compositions containing secretome

Abstract

The present invention provides compositions useful for inducing immune responses, treating inflammatory responses, treating microbial infections, cell differentiation, wound healing, embryogenesis, placental development, central nervous system development, or morphogenesis. [Solution] A composition is provided comprising 1) a secretome of about 0.1 w / w% or more, and 2) an excipient acceptable as a pharmaceutical or cosmetic, wherein the secretome comprises MCP-1 and the composition does not contain cells.

Description

[Technical Field]

[0001]

[0001] Cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 020,250, filed on 5 May 2020, which is incorporated herein by reference in its entirety. [Background technology]

[0002]

[0002] Incorporation by reference All publications, patents, and patent applications herein are incorporated by reference to the same extent as any individual publication, patent, or patent application is explicitly indicated to be incorporated by reference. In the event of any inconsistency between the terminology herein and the terminology in any incorporated reference, the terminology herein shall prevail. [Overview of the Initiative]

[0003]

[0003] The embodiments of the invention provided in this brief summary are for illustrative purposes only and are intended to provide an overview of the selected embodiments disclosed herein. This brief summary is descriptive and selective and does not limit any claims, does not provide the full scope of the embodiments of the invention disclosed or envisioned herein, and should not be construed as limiting or restricting the scope of the disclosure or any claimed embodiments of the invention.

[0004]

[0004] The secretomes disclosed herein may include chemokines, interleukins, growth factors, or any combination thereof. The secretomes disclosed herein may include microvesicles, exosomes, or combinations thereof. In some of the many embodiments, compositions are disclosed herein that comprise 1) about 0.1 w / w% or more of a secretome and 2) excipients acceptable as pharmaceuticals or cosmetics, wherein the secretome comprises monocyte chemotactic protein-1 (MCP-1; CCL2) and is cell-free. In some examples, the secretome comprises MCP-1 and one or more of the chemokine (CXC motif) ligand 2 (CXCL2; GRO), interleukin 6 (IL-6), IL-8, and vascular endothelial growth factor (VEGF) proteins. In some examples, the secretome comprises MCP-1 and two or more of the CXCL2 (GRO), IL-6, IL-8, and VEGF proteins. In some cases, the secretome contains MCP-1 and three or more of the following proteins: CXCL2(GRO), IL-6, IL-8, and VEGF. In some cases, the secretome contains MCP-1 and all of the following proteins: CXCL2(GRO), IL-6, IL-8, and VEGF.

[0005]

[0005] The secretome may constitute at least 0.6%, 1%, 1.25%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of the composition. In some examples, the secretome may constitute about 0.6%, about 1%, about 1.25%, about 1.5%, about 2%, about 2.5%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% of the composition. In some cases, the secretome constitutes about 0.6% to about 25% of the composition, or about 2.5% to about 10% of the composition. In some cases, the composition is a liquid or gel containing about 100 ng / ml to about 200 ng / ml of MCP-1.

[0006]

[0006] In some embodiments, one or more of MCP-1 and IL-6, VEGF, platelet-derived growth factor AA (PDGF-AA), IL-8, or CXCL2 (GRO) are used. A composition comprising further proteins and excipients acceptable as pharmaceuticals or cosmetics is disclosed herein, wherein the ratio of MCP-1 to further proteins is in the range of about 30:1 to about 60:1.

[0007]

[0007] In some embodiments, compositions comprising a secretome and excipients acceptable as pharmaceuticals or cosmetics are disclosed herein, wherein the secretome comprises MCP-1 and one or more further proteins selected from IL-6, VEGF, PDGF-AA, IL-8, or CXCL2(GRO). Alternatively, compositions comprising a secretome and excipients acceptable as pharmaceuticals or cosmetics are disclosed herein, wherein the secretome comprises MCP-1, CXCL2(GRO), and one or more further proteins selected from IL-8, MCP-3, IL-6, G-CSF, or VEGF. For example, the ratio of MCP-1 to IL-8 is in the range of approximately 10:1 to 7:1, the ratio of MCP-1 to MCP-3 is in the range of approximately 10:1 to 30:1, the ratio of MCP-1 to IL-6 is in the range of approximately 30:1 to 50:1, the ratio of MCP-1 to G-CSF is in the range of approximately 30:1 to 50:1, the ratio of MCP-1 to VEGF is in the range of approximately 30:1 to 50:1, and CXCL2 and I The ratio of L-8 is in the range of approximately 3:1 to approximately 4:1, the ratio of CXCL2 to MCP-3 is in the range of approximately 5:1 to approximately 15:1, the ratio of CXCL2 to IL-6 is in the range of approximately 10:1 to approximately 20:1, and / or the ratio of CXCL2 to G-CSF is in the range of approximately 10:1 to approximately 20:1, the ratio of CXCL2 to VEGF is in the range of approximately 10:1 to approximately 20:1, or any combination thereof.

[0008]

[0008] In some embodiments, compositions comprising liposomes and excipients acceptable as pharmaceuticals or cosmetics, wherein the liposomes comprise phospholipids and secretomes, and the compositions are cell-free. The secretomes can be encapsulated within the liposomes. Alternatively, the liposomes can be in the form of nanoparticles. In some examples, the nanoparticles have an average particle size of about 10 to about 400 nanometers. In some examples, the nanoparticles have an average particle size of about 50 to about 300 nanometers. In some examples, the nanoparticles have an average particle size of about 100 to about 200 nanometers.

[0009]

[0009] In some cases, exosomes harbor chemokines including CXCL2 (GRO), MCP-1, fractalkines, interferon-gamma-inducible protein 10 (IP-10), MCP-3, eotaxin, macrophage inflammatory protein-1β (MIP-1β), or any combination thereof. In some cases, exosomes harbor interleukins including IL-6, IL-8, IL-4, IL-1RA, IL-10, IL-12P40, IL-15, IL-1α, IL-17A, or any combination thereof. In some cases, exosomes harbor growth factors including PDGF-AA, VEGF, bFGF, G-CSF, Flt-3L, GM-CSF, or any combination thereof. In some cases, the secretome contains MCP-1 and one, two, three, or all of the following proteins: CXCL2 (GRO), IL-6, IL-8, and VEGF. In some cases, the secretome contains MCP-1 and CXCL2 in a weight ratio of approximately 1:1 to approximately 2:1. In some cases, the secretome contains MCP-1 and CXCL2 in a weight ratio of approximately 3:1 to approximately 4:1. In some cases, the secretome contains MCP-1 and IL-6 in a weight ratio of approximately 2:1 to approximately 3:1. In some cases, the secretome contains MCP-1 and IL-6 in a weight ratio of approximately 3:1 to approximately 4:1. In some cases, the secretome contains MCP-1 and IL-8 in a weight ratio of approximately 4:1 to approximately 6:1. In some cases, the secretome contains MCP-1 and VEGF in a weight ratio of approximately 4:1 to approximately 6:1. In some cases, the secretome contains MCP-1 and VEGF in a weight ratio of approximately 7:1 to approximately 9:1. In some cases, the secretome further contains PDGF-AA, with MCP-1 and PDGF-AA present in the secretome in a weight ratio of approximately 3:1 to approximately 5:1. In some cases, the secretome further contains PDGF-AA, with MCP-1 and PDGF-AA present in the secretome in a weight ratio of approximately 6:1 to approximately 9:1. In some cases, the secretome further contains PDGF-AA, with MCP-1 and PDGF-AA present in the secretome in a weight ratio of approximately 30:1 to approximately 60:1. In some cases, the ratio of MCP-1 to any one of the proteins CXCL2, IL-6, IL-8, and VEGF is in the range of approximately 30:1 to approximately 60:1. In some cases, the secretome contains the proteins MCP-1, CXCL2, IL-6, IL-8, and VEGF. In some cases, the secretome contains MCP-1, CXCL2 (GRO), and one, two, three, four, or all of the proteins IL-8, MCP-3, IL-6, G-CSF, and VEGF. In some cases, the secretome contains MCP-1 and CXCL2 in a weight ratio of approximately 2:1 to approximately 3:1. In some cases, the secretome further contains IL-8, with an MCP-1 to IL-8 ratio ranging from approximately 10:1 to approximately 6:1 and / or a CXCL2 to IL-8 ratio ranging from approximately 3:1 to approximately 4:1. In some cases, the secretome further contains MCP-3, with an MCP-1 to MCP-3 ratio ranging from approximately 10:1 to approximately 30:1 and / or a CXCL2 to MCP-3 ratio ranging from approximately 5:1 to approximately 15:1. In some cases, the secretome further contains IL-6, with an MCP-1 to IL-6 ratio ranging from approximately 30:1 to approximately 50:1 and / or a CXCL2 to IL-6 ratio ranging from approximately 10:1 to approximately 20:1. In some cases, the secretome further contains G-CSF, with an MCP-1 to G-CSF ratio in the range of approximately 30:1 to approximately 50:1 and / or a CXCL2 to G-CSF ratio in the range of approximately 10:1 to approximately 20:1. In some cases, the secretome further contains VEGF, with an MCP-1 to VEGF ratio in the range of approximately 30:1 to approximately 50:1 and a CXCL2 to VEGF ratio in the range of approximately 10:1 to approximately 20:1. In some examples, the compositions further include one or more proteins from among IP-10, eotaxin, Flt-3L, GM-CSF, MIP-1a, MIP-1b, IL-1a, IL-1RA, IL-4, IL-7, IL-10, IL-12P40, IL-13, IL-15, IL-17A, CCL5(RANTES), MDC, MCP-3, IL-12P70, IFN-alpha, IFNR, PDGF-AB / BB, or EGF.

[0010]

[0010] Alternatively, the compositions disclosed herein may further include a hydrophilic surfactant. Alternatively, the compositions may further include a vitamin. Alternatively, the compositions may further include a hydrophobic surfactant. Alternatively, the compositions may further include a fatty acid molecule. Alternatively, the compositions may further include linoleic acid. Alternatively, the compositions may further include collagen. Alternatively, the compositions may further include hyaluronic acid. Alternatively, the compositions may further be free of serum, antibiotics, or any combination thereof. Alternatively, the compositions may further be free of steroids, cholesterol, choline chloride, hypoxanthine sodium salt, thymidine, putrescine dihydrochloride, ferric nitrate, L-glutamine, or any combination thereof. Alternatively, the compositions may further be free of color additives.

[0011]

[0011] The compositions described herein may be suitable for administration as medicinal cosmetic compositions or pharmaceutical compositions. In some examples, the compositions are in the form of lotions, creams, liquids, gels, emulsions, suspensions, pastes, sticks, aerosols, foams, patches, powders, ointments, beads, masks, pads, sheets, wound dressings, bandages, or any combination thereof. In some examples, excipients acceptable as pharmaceuticals or cosmetics include sterile water, phosphate-buffered saline, surfactants, glycerol, seed oils, fruit oils, flower extracts, mineral oils, synthetic oils, saccharides, silicates, calcium salts, magnesium salts, sodium chloride, sodium hydroxide, potassium chloride, lactose, lactic acid, starch, sugar alcohols, cellulose, activated carbon, amino acids, paraffin, honey, wax, beeswax, agar, calcium carbonate, citric acid, tartaric acid, steric acid, xanthan gum, benzoic acid or its salts, polyethylene glycol, silicone, or any combination thereof.

[0012]

[0012] In some embodiments, methods disclosed herein include the step of bringing a composition disclosed herein into contact with an object that requires contact with the composition. In some examples, the method treats a disease in the object. In some examples, the method improves the condition of the skin of the object. In some examples, the disease or condition is eczema, rash, psoriasis, acne, rosacea, ichthyosis, vitiligo, urticaria, seborrheic dermatitis, herpes zoster, burns, sunburn, contact dermatitis, wrinkled skin, scarred skin, loose skin, loss of skin elasticity, dry skin, dull skin, or any combination thereof.

[0013]

[0013] In one embodiment, a method for producing one or more proteins of interest derived from trophoblast cell lines is provided herein, comprising the steps of: culturing human trophoblast stem cells in a nutrient medium until a culture density is reached; inducing hypoxia; and isolating the one or more proteins of interest from the medium. In some examples, hypoxia is induced for approximately 12 to 48 hours, and in some examples, for about 24 hours. The culture density can be varied depending on the culture dish being used. A non-limiting example of a culture density is about 3,000 cells / cm³. 2 ~about 9,000 cells / cm 2 , about 4,000 cells / cm 2 ~about 8,000 cells / cm 2 , about 5,000 cells / cm 2 ~about 7,000 cells / cm 2 , or approximately 6,000 cells / cm² 2 This may include: In some examples, one or more isolated proteins may be further mixed with one or more pharmaceutically acceptable excipients, as needed, to prepare a composition.

[0014]

[0014] The described method can produce one or more proteins that include cytokines, growth factors, membrane-bound signaling molecules, cell adhesion molecules, protective proteins, immune proteins, and extracellular matrix proteins, intracellular signaling molecules, metabolite interconversion enzymes, protein modifying enzymes / proteases, protein-binding modulators / protease inhibitors, scaffold / adapter proteins, structural proteins, transport proteins or carrier proteins, transmembrane signaling receptors, or any combination thereof.The secretome produced from any one of the described methods is used in the following processes: biological adhesion / cell adhesion, bioregulation, cell proliferation, cellular component organization or biodevelopment, cellular processes (e.g., cell activation, cell communication, cell cycle processes, cell death, cell growth, cellular component organization, cell development processes, cell differentiation, cellular component morphogenesis, cellular metabolic processes, cellular responses to stimuli, export from cells, microtubule-based processes, cell activation, cell communication, cell cycle processes, cell death, cell growth, cellular component organization, cell development processes (e.g., cell differentiation or cellular component morphogenesis), cellular metabolic processes, cellular responses to stimuli, export from cells, microtubule-based processes, movement of cells or subcellular components, cell motility, neuronal projection guidance, myelin formation, signal transduction, etc.), developmental processes (e.g., anatomical structures). It is useful in one or more of the following processes: expression, anatomical structure formation involved in morphogenesis, anatomical structure morphogenesis, cell development processes, development and growth, etc.), growth, immune system processes (e.g., immune effector processes, immune responses, immune system development, leukocyte activation, leukocyte migration, etc.), localization (e.g., cell localization, establishment of localization, cell localization, macromolecule localization, etc.), movement (e.g., cell motility, chemotaxis, etc.), metabolic processes (e.g., biosynthesis processes, catabolism processes, cellular metabolic processes, hormone metabolic processes, nitrogen compound metabolic processes, etc.), multicellular processes / responses to other organisms, multicellular biological processes (e.g., coagulation, cytokine production, digestion, multicellular organism development, system processes, etc.), responses to stimuli (e.g., cellular responses to stimuli, immune responses, etc.), and signal transduction (e.g., intercellular signal transduction, signal transduction, etc.).

[0015]

[0015] The secretome produced by any one of the described methods is transmitted through the following pathways: Alzheimer's disease-amyloid secretion pathway; Alzheimer's disease-presenilin pathway; angiogenesis; apoptosis signaling pathway; Slit / Robo-mediated axonal guidance; Netrin-mediated axonal guidance; blood coagulation; CCKR signaling pathway. It is useful in one or more of the following pathways: cadherin signaling pathway; endothelin signaling pathway; FAS signaling pathway; gonadotropin-releasing hormone receptor pathway; inflammation mediated by chemokine and cytokine signaling pathways; insulin / IGF pathway-MAPKK / MAPK cascade; insulin / IGF pathway-PKB signaling cascade; interleukin signaling pathway; PDGF signaling pathway; plasminogen activation cascade; T cell activation; TGF-beta signaling pathway; Toll receptor signaling pathway; Wnt signaling pathway; p53 pathway, etc.

[0016]

[0016] A method is provided herein that includes the step of administering one of such compositions to a subject requiring administration of the composition. The use of one of the compositions for treating a subject requiring treatment, or for the manufacture of a pharmacopoeia for treating a subject requiring treatment is provided herein. The use of one of the compositions for use in in vitro culture or assay is provided herein.

[0017]

[0017] In any of the compositions, the composition may be substantially free of cells. Or, the composition may be free of cells.

[0018]

[0018] The secretome can be present in the composition in amounts of approximately 0.1% to approximately 75% by weight, approximately 0.1% to approximately 65% ​​by weight, approximately 0.1% to approximately 50% by weight, approximately 0.1% to approximately 40% by weight, approximately 0.1% to approximately 30% by weight, approximately 0.1% to approximately 20% by weight, approximately 0.1% to approximately 15% by weight, approximately 0.1% to approximately 10% by weight, or approximately 0.1% to approximately 5% by weight.

[0019]

[0019] In any of the embodiments, the secretome can constitute at least 0.6%, 1%, 1.25%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of the composition. In some examples, the secretome constitutes about 0.6%, about 1%, about 1.25%, about 1.5%, about 2%, about 2.5%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% of the composition. In some examples, the secretome constitutes about 0.6% to about 25% of the composition, or about 2.5% to about 10% of the composition.

[0020]

[0020] When the secretome contains more than one protein, each protein can be present in a ratio of about 1:1 to about 20:1. For example, each protein can be present in a ratio of about 1:1, about 2:1, about 3:1, about 4:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1, about 10:1, about 11:1, about 12:1, about 13:1, about 14:1, about 15:1, about 16:1, about 17:1, about 18:1, about 19:1, or about 20:1.

[0021]

[0021] In some cases, the compositions disclosed herein can be sterile. In some cases, the compositions can contain one or more commensal microorganisms or cells. One or more microorganisms or cells can be viruses, bacteria, eukaryotic cells, or any combination thereof. In some examples, one or more microorganisms or cells may not be pathogenic. In some examples, the compositions can contain bacteria (one or more) at concentrations of 10 colony-forming units (CFU) / gram (g), 50 CFU / g, 100 CFU / g, 150 CFU / g, 200 CFU / g, 300 CFU / g, 400 CFU / g, 500 CFU / g, 600 CFU / g, 700 CFU / g, 800 CFU / g, 900 CFU / g, or less than 1000 CFU / g. In some cases, the composition contains bacteria at approximately 10 CFU / g to 1000 CFU / g, approximately 10 CFU / g to 50 CFU / g, and approximately 20 CFU / The composition may contain concentrations of approximately 100 CFU / g, 50 CFU / g to 200 CFU / g, 100 CFU / g to 250 CFU / g, 200 CFU / g to 500 CFU / g, 500 CFU / g to 700 CFU / g, or 600 CFU / g to 1000 CFU / g. In some cases, the composition may be substantially free of Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Pseudomonas species, Klebsiella pneumoniae, or any combination thereof, or may not contain any of these bacteria.

[0022] In some cases, the compositions disclosed herein may not contain, for example, heavy metals such as lead, bithionol, chlorofluorocarbon propellants, nitrosoamines, chloroform, halogenated salicylanilide, hexachlorophene, mercury compounds, 1,4-dioxane, methylene chloride, prohibited bovine materials, sunscreen compounds, vinyl chloride, zirconium-containing complexes, or any combination thereof. In some examples, the prohibited bovine materials can include the brain, skull, eyeball, trigeminal ganglion, spinal cord, vertebral column, dorsal root ganglion, tonsils, distal ileum of the small intestine, or any combination thereof. In some examples, the composition may contain lead at a level of less than 10 parts per million (ppm).

[0023] In some cases, the compositions of the present specification do not contain color additives. In some cases, the composition can contain color additives. In some cases, the composition may contain incidental components such as color additives at levels insufficient to incorporate into the composition, for example, less than 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1%. In some cases, the incidental components may have no technical / structural, functional, or any combination of effects in the composition, for example, the incidental components are not active ingredients.

[0024]

[0024] In some examples, the composition protein is divided into 1 nanogram / milliliter (ng / ml), 2 ng / ml, 3 ng / ml, 4 ng / ml, 5 ng / ml, 6 ng / ml, 7 ng / ml, 8 ng / ml, 9 ng / ml, 10 ng / ml, 11 ng / ml, 12 ng / ml, 13 ng / ml, 14 ng / ml, 15 ng / ml, 16 ng / ml, 17 ng / ml, 18 ng / ml, 19 ng / ml, 20 ng / ml, 21 ng / ml, 22 ng / ml, 23 ng / It can contain concentrations of 24 ng / ml, 25 ng / ml, 30 ng / ml, 35 ng / ml, 40 ng / ml, 45 ng / ml, 50 ng / ml, 60 ng / ml, 70 ng / ml, 80 ng / ml, 90 ng / ml, 100 ng / ml, 200 ng / ml, 300 ng / ml, 400 ng / ml, 500 ng / ml, 600 ng / ml, 700 ng / ml, 800 ng / ml, 900 ng / ml, 1000 ng / ml, or less than 10000 ng / ml. In some examples, the composition can contain protein at concentrations of approximately 1 ng / ml to 100 ng / ml, approximately 10 ng / ml to 200 ng / ml, approximately 10 ng / ml to 400 ng / ml, approximately 50 ng / ml to 300 ng / ml, approximately 100 ng / ml to 200 ng / ml, approximately 150 ng / ml to 400 ng / ml, approximately 200 ng / ml to 600 ng / ml, approximately 400 ng / ml to 700 ng / ml, approximately 500 ng / ml to 900 ng / ml, approximately 600 ng / ml to 1000 ng / ml, approximately 900 ng / ml to 1500 ng / ml, or approximately 1000 ng / ml to 10000 ng / ml.

[0025]

[0025] In some examples, the secretome can constitute at least 0.01%, 0.1%, 1%, 1.25%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% of the composition. In some examples, the secretome can constitute about 0.01% to about 0.1%, about 0.01% to about 1%, about 1% to about 2%, or about 1% to about 5% of the composition. It can constitute approximately 3% to 8% of the composition, approximately 5% to 10% of the composition, approximately 10% to 20% of the composition, approximately 20% to 40% of the composition, approximately 30% to 50% of the composition, approximately 50% to 75% of the composition, approximately 60% to 90% of the composition, approximately 75% to 95% of the composition, or approximately 80% to 99% of the composition.

[0026]

[0026] In some cases, the compositions described herein may include exosomes, liposomes, nanoparticles, or any combination thereof. In some examples, liposomes may be in the form of nanoparticles. In some examples, nanoparticles may include liposomes. In some cases, exosomes, liposomes, nanoparticles, or any combination thereof may include secretomes, phospholipids, proteins, hydrophilic surfactants, hydrophilic surfactants, vitamins, inactive components, or any combination thereof. Liposomes may include, but are not limited to, monolayer liposomes, multilayer liposomes, archaeosomes, noisomes, novasomes, cryptosomes, emulsomes, vesosomes, nanoliposomes, nanoemulsions, or derivatives of any of these, or any combination thereof. Nanoparticles may include, but are not limited to, biopolymer nanoparticles, alginate nanoparticles, xanthan gum nanoparticles, cellulose nanoparticles, lipid nanoparticles, dendrimers, polymer micelles, polyplexed nanoparticles, inorganic nanoparticles, nanocrystals, metal nanoparticles, quantum dots, protein nanoparticles, polysaccharide nanoparticles, derivatives of any of these, or any combination thereof.

[0027]

[0027] In some examples, nanoparticles can be 1 nanometer (nm), 2 nm, 3 nm, 4 nm, 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, 15 nm, 16 nm, 17 nm, 18 nm, 19 nm, 20 nm, 21 nm, 22 nm, 23 nm, 24 nm, 25 nm, 26 nm, 27 nm, 28 nm, 29 nm, 30 nm, 35 nm, 40 nm, 45 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 200 nm, 300 nm, 400 nm, 500 nm, 600 nm, 700 nm, 800 nm, 900 nm, or less than 1000 nm. In some cases, nanoparticles can be larger than 1 nanometer (nm), 2nm, 3nm, 4nm, 5nm, 6nm, 7nm, 8nm, 9nm, 10nm, 11nm, 12nm, 13nm, 14nm, 15nm, 16nm, 17nm, 18nm, 19nm, 20nm, 21nm, 22nm, 23nm, 24nm, 25nm, 26nm, 27nm, 28nm, 29nm, 30nm, 35nm, 40nm, 45nm, 50nm, 60nm, 70nm, 80nm, 90nm, 100nm, 200nm, 300nm, 400nm, 500nm, 600nm, 700nm, 800nm, 900nm, or 1000nm. In some cases, nanoparticles can have average particle sizes of approximately 1 nm to 100 nm, 10 nm to 200 nm, 10 nm to 400 nm, 50 nm to 300 nm, 100 nm to 200 nm, 150 nm to 400 nm, 200 nm to 600 nm, 400 nm to 700 nm, 500 nm to 900 nm, 600 nm to 1000 nm, or 700 nm to 1500 nm.

[0028]

[0028] In any of the embodiments, examples, and / or examples, the inventors have demonstrated that the stem cells are immune-privileged, chromosomally stable (non-tumorogenic), pathogen-free, and pluripotent. The inventors have also demonstrated efficient differentiation of their stem cells into programmed natural killer (NK), cartilage, bone, adipose, nerve, pancreatic, liver, and secretome cells, with remarkable doubling time and growth characteristics.

[0029]

[0029] Various aspects of the present invention are specifically described in the appended claims. A better understanding of the features and advantages of the present invention is provided by describing exemplary embodiments in which the principles of the present invention are utilized. This can be obtained by referring to the following detailed explanation and its accompanying drawings. [Brief explanation of the drawing]

[0030] [Figure 1A] Figures 1A-1D show the secretome composition profiles. Figure 1A represents hTSC secretome secretion based on the average of two cell lines minus a negative control consisting of only culture medium. The graph shows the highest protein concentration and is sorted in descending order. Figure 1B represents prCTB from hTSCs and pancreatic progenitor cells (with bFGF for 24 hours). The prCTB / PPC secretion is based on the average of two cell lines (1808 and 1808-3E2 monoclones) minus a negative control consisting of only culture medium. The graph shows the highest protein concentration and is sorted in descending order. Figure 1C represents neural progenitor cells (with RA for 24 hours) from hTSCs. NSC secretion is based on the average of two cell lines (1808 and 1808-3E2 monoclones) minus a negative control consisting of only culture medium. The graph shows the highest protein concentration and is sorted in descending order. Figure 1D shows hepatocyte-like cells derived from hTSCs (8h+Dexa with bFGF, 5-7d with OSM, BMP4, and HGF). HPC secretion is based on the average of two cell lines (1808 and 1808-3E2 monoclones) minus the negative control (culture medium only). The graph shows the highest protein concentration and is sorted in descending order. [Figure 1B] The explanation is the same as for Figure 1A. [Figure 1C] The explanation is the same as for Figure 1A. [Figure 1D] The explanation is the same as for Figure 1A. [Figure 2A]

[0030] Figures 2A-2C show further secretome composition profiles. Figure 2A represents neural progenitor cells derived from hTSC (with RA for 24 hours). The NSC secretion data is the same as that from Figure 1C, and is more finely subgrouped into chemokines, cytokines, and growth factors. Figure 2B represents prCTB and pancreatic progenitor cells derived from hTSC (with bFGF for 24 hours). The prCTB / PPC secretion data is the same as that from Figure 1B, and is more finely subgrouped into chemokines, cytokines, and growth factors. Figure 2C represents hepatocyte-like cells derived from hTSC (with bFGF for 8 hours + Dexa, with OSM, BMP4, and HGF for 5-7 days). The HPC secretion data is the same as that from Figure 1D, and is more finely subgrouped into chemokines, cytokines, and growth factors. [Figure 2B] The explanation is the same as for Figure 2A. [Figure 2C] The explanation is the same as for Figure 2A. [Figure 3]

[0031] Figure 3 shows the results of an MTT assay of skin cell viability in the presence of exemplary secretome formulations as described herein. Cell viability is shown at 48 hours (solid bars), 72 hours (shaded bars), or 96 hours (slashed bars) for various concentrations of secretome formulations compared to the control. * = statistical significance compared to the control. [Figure 4]

[0032] Figure 4A is a bar graph showing the results of a skin cell transwell migration assay compared to a control at 4, 6, and 8 hours of culture in the presence of MCP-1. Figure 4B is an electron microscope image showing control versus MCP-1 at 4, 6, and 8 hours of culture. [Modes for carrying out the invention]

[0031] Detailed explanation

[0033] Details of one or more embodiments of the invention are provided in the attached drawings, claims, and The features, compounds, compositions, methods, and advantages of the disclosure of the present invention as described herein may be combined with any other features, compounds, compositions, methods, and advantages disclosed herein unless expressly excluded.

[0032]

[0034] Unless otherwise specified, all technical terms and scientific terms used herein are excluded. The terms have the same meaning as generally understood by those skilled in the art to the subject matter claimed. The above general description and the following detailed description, which are expected to be understood as such, are illustrative and descriptive only and do not limit any subject matter claimed. In this application, the use of the singular form includes the plural form unless otherwise specified. It should be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include the plural referent unless the context clearly indicates otherwise. In this application, the use of "or" means "and / or" unless otherwise specified. Furthermore, the use of the term "including," and other forms such as "include," "includes," and "included," is non-limiting.

[0033]

[0035] When used herein, ranges and quantities are expressed as "approximate" specific values ​​or ranges, for example, ±15% of the mentioned number. "Approximately" also includes exact quantities; for example, "approximately 5 μL" means "approximately 5 μL" and also "5 μL". Generally, the term "approximately" includes quantities expected to be within experimental error.

[0034]

[0036] The terms “to treat” and “treatment” are used herein to mean obtaining a desired pharmacological and / or physiological effect. In some cases, an individual is treated therapeutically (e.g., if an individual has a liver-related disease or disorder), and such therapeutic treatment results in a partial or complete cure or treatment of the disease or disorder, and / or reverses adverse effects caused by the disease or disorder, and / or stabilizes the disease or disorder, and / or delays the progression of the disease or disorder, and / or results in remission of the disease or disorder. In some cases, a subject is treated prophylactically (e.g., an individual suspected of having a liver-related disease or disorder, and / or genetically predisposed thereto, is treated prophylactically with the cell preparations described herein), and such prophylactic treatment completely or partially prevents the liver-related disease or disorder or its signs or symptoms.

[0035]

[0037] Administration to areas requiring the treatment disclosed herein can be achieved, for example, by local infusion (e.g., during surgery), injection, catheter, or implant. The implant may be made of porous, non-porous, or gel-like material, but may be a membrane or fiber, such as a sialastic membrane.

[0036]

[0038] An "effective dose" is the amount of therapeutic agent sufficient to achieve the intended purpose. An effective dose of a composition for treating or alleviating a disease or disorder is the amount of the composition sufficient to reduce or eliminate the symptoms of the disease or disorder.

[0037]

[0039] The chapter headings used herein are for systematization purposes only and should not be construed as limiting the subjects described.

[0038] composition

[0040] In some embodiments, cells or populations of cells (e.g., stem cells in the examples) are separated. Compositions comprising secreted secretomes, such as proteins, exosomes, and microvesicles, are disclosed herein. In some cases, the stem cells may be pluripotent. In some cases, the stem cells may be mortal. In some cases, the stem cells may not be embryonic stem cells. In some cases, the stem cells may be derived from trophoblast tissue. In some cases, the stem cells may be lethal pluripotent stem cells or cells differentiated therefrom. In some cases, the secretome is isolated or purified and is not present in the host organism or stem cells from which the secretome originates. The secretome is purified or extracted from a stem cell culture or culture medium. In some cases, the secretome may be one or more proteins comprising cytokines, chemokines, growth factors, soluble molecules, or any combination thereof. In some cases, one or more proteins may be isolated from exosomes or microparticles. In some cases, one or more proteins may be on the surface of exosomes or microparticles. In some cases, one or more proteins may be encapsulated by exosomes or microparticles. In some cases, the exosomes may have an average particle size of less than about 500 nm, e.g., less than about 250 nm, or e.g., about 50 to about 150 nm. In some cases, the composition may contain one or more excipients that are acceptable as pharmaceuticals and / or cosmetics.

[0039]

[0041] A composition comprising 1) about 0.1 w / w% or more of a secretome and 2) an excipient acceptable as a pharmaceutical or cosmetic is disclosed herein, wherein the secretome comprises MCP-1 and is cell-free. A medicated cosmetic composition comprising 1) about 0.1 w / w% or more of a secretome and 2) one or more excipients acceptable as a cosmetic is disclosed herein, wherein the secretome comprises MCP-1 and is cell-free. A pharmaceutical composition comprising 1) about 0.1 w / w% or more of a secretome and 2) one or more excipients acceptable as a pharmaceutical is disclosed herein, wherein the secretome comprises MCP-1 and one of the proteins CXCL2(GRO), IL-6, IL-8, and VEGF. In some cases, the secretome comprises MCP-1 and two of the following proteins: CXCL2(GRO), IL-6, IL-8, and VEGF. In some cases, the secretome comprises MCP-1 and three of the following proteins: CXCL2(GRO), IL-6, IL-8, and VEGF. In some cases, the secretome comprises MCP-1 and all of the following proteins: CXCL2(GRO), IL-6, IL-8, and VEGF. In some cases, the secretome constitutes at least 0.6%, 1%, 1.25%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of the composition. In some cases, the secretome constitutes about 0.6%, about 1%, about 1.25%, about 1.5%, about 2%, about 2.5%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% of the composition. In some cases, the secretome constitutes about 0.6% to about 25% of the composition. In some cases, the secretome constitutes about 2.5% to about 10% of the composition. In some cases, the composition is a liquid or gel and contains about 100 ng / ml to about 200 ng / ml of secretome protein, such as MCP-1.In some cases, secretome proteins may be present in the composition in amounts of approximately 0.1–1 ng / ml, approximately 1–100 ng / ml, approximately 20–100 ng / ml, approximately 200–500 ng / ml, or approximately 500–1000 ng / ml. If more than one protein is present in the composition, each protein may be present in the composition in amounts of approximately 0.1–1 ng / ml, 1–100 ng / ml, 20–100 ng / ml, 200–500 ng / ml, or 500–1000 ng / ml. Alternatively, if more than one protein is present in the composition, all of the combined proteins may be present in the composition in amounts of approximately 0.1–1 ng / ml, 1–100 ng / ml, 20–100 ng / ml, 200–500 ng / ml, or 500–1000 ng / ml.

[0040]

[0042] In some embodiments, a composition comprising MCP-1 and one or more additional proteins selected from IL-6, VEGF, PDGF-AA, IL-8, or CXCL2(GRO); and excipients acceptable as pharmaceuticals or cosmetics, wherein MCP-1 Compositions are disclosed herein in which the weight ratio of MCP-1 to each of one or more additional proteins is in the range of about 30:1 to about 60:1, for example, about 30:1 to about 50:1, about 30:1 to about 40:1, or about 40:1 to about 50:1. In some cases, MCP-1 is present in the composition in an amount of about 1 to 20 ng / ml, for example, 1 to 10 ng / ml, for example, about 6 to 7 ng / ml.

[0041]

[0043] A composition comprising MCP-1 and one or more additional proteins from among IL-6, VEGF, PDGF-AA, IL-8, or CXCL2(GRO); and an excipient composition acceptable as a pharmaceutical or cosmetic is disclosed herein. Alternatively, a composition comprising MCP-1 and CXCL2(GRO), and one or more additional proteins from among IL-8, MCP-3, IL-6, G-CSF, or VEGF; and an excipient acceptable as a pharmaceutical or cosmetic is disclosed herein. In any of these compositions, the ratio of MCP-1 to IL-8 in the secretome or composition is in the range of approximately 10:1 to approximately 7:1, the ratio of MCP-1 to MCP-3 in the secretome or composition is in the range of approximately 10:1 to approximately 30:1, the ratio of MCP-1 to IL-6 in the secretome or composition is in the range of approximately 30:1 to approximately 50:1, the ratio of MCP-1 to G-CSF in the secretome or composition is in the range of approximately 30:1 to approximately 50:1, and the ratio of MCP-1 to VEGF in the secretome or composition is in the range of approximately 30:1 to approximately 50:1. The ratio of CXCL2 to IL-8 in the secretome or composition is in the range of approximately 3:1 to approximately 4:1, the ratio of CXCL2 to MCP-3 in the secretome or composition is in the range of approximately 5:1 to approximately 15:1, the ratio of CXCL2 to IL-6 in the secretome or composition is in the range of approximately 10:1 to approximately 20:1, the ratio of CXCL2 to G-CSF in the secretome or composition is in the range of approximately 10:1 to approximately 20:1, the ratio of CXCL2 to VEGF in the secretome or composition is in the range of approximately 10:1 to approximately 20:1, or any combination thereof. In some cases, MCP-1 is present in the secretome or composition in amounts of approximately 1 to 20 ng / ml, approximately 1 to 10 ng / ml, or approximately 6 to 7 ng / ml.

[0042]

[0044] In some cases, compositions herein, which include secretome proteins such as MCP-1, CXCL2, and IL-8, but are not limited thereto, can facilitate immune responses such as wound healing and / or angiogenesis.

[0043]

[0045] In some cases, compositions herein that include secretome proteins such as IL-6 can stimulate energy mobilization resulting in increased circulation in muscle and / or adipose tissue.

[0044]

[0046] In some cases, compositions herein, including secretome proteins such as PDGF, can regulate cell proliferation and division in blood vessels, proliferation of blood vessels from existing vascular tissue, mitotic induction, such as proliferation, of mesenchymal cells, such as fibroblasts, osteoblasts, tenocytes, vascular smooth muscle cells, and mesenchymal stem cells, as well as chemotaxis and directed migration of mesenchymal cells.

[0045]

[0047] In some cases, compositions herein, including secretome proteins such as VEGF, can facilitate angiogenesis (de novo formation of the fetal circulatory system) and neovascularization (proliferation of blood vessels from the existing vascular system) after injury, or restore oxygen supply to tissues in cases of insufficient blood circulation, such as hypoxic conditions.

[0046]

[0048] In some cases, the compositions herein, though not limited to, include, but are effective in inducing inflammation (e.g., ROS-mediated), granular ECM formation, wound closure, and / or ECM regeneration. This can facilitate one or more stages of wound healing, such as structural reinforcement and remodeling.

[0047]

[0049] In some embodiments, compositions comprising liposomes and excipients acceptable as pharmaceuticals or cosmetics, wherein the liposomes comprise phospholipids and secretomes, and the compositions are cellular or substantially cellular. In some cases, the secretomes are encapsulated within the liposomes. In some cases, the liposomes are in the form of nanoparticles. In some cases, the nanoparticles have an average particle size of about 10 to about 400 nanometers. In some cases, the nanoparticles have an average particle size of about 50 to about 300 nanometers. In some cases, the nanoparticles have an average particle size of about 100 to about 200 nanometers.

[0048]

[0050] In some cases, the secretome comprises chemokines, interleukins, growth factors, or any combination thereof. In some cases, the secretome comprises microvesicles, exosomes, or any combination thereof. In some cases, the exosomes comprise chemokines, which include CXCL2, MCP-1, fractalkine, IP-10, MCP-3, eotaxin, MIP-1β, or any combination thereof. In some cases, the exosomes comprise interleukins, which include IL-6, IL-8, IL-4, IL-1RA, IL-10, IL-12P40, IL-15, IL-1α, IL-17A, or any combination thereof. In some cases, the exosomes comprise growth factors, which include PDGF-AA, VEGF, bFGF (FGF-2), G-CSF, Flt-3L, GM-CSF, or any combination thereof. In some cases, the secretome contains one, two, three, or all of the following proteins: MCP-1 and CXCL2 (GRO), IL-6, IL-8, and VEGF proteins. In some cases, the secretome contains MCP-1 and CXCL2 in a weight ratio of approximately 1:1 to approximately 2:1. Alternatively, or in addition, the secretome contains MCP-1 and CXCL2 in a weight ratio of approximately 3:1 to approximately 4:1. Alternatively, or in addition, the secretome contains MCP-1 and IL-6 in a weight ratio of approximately 2:1 to approximately 3:1. Alternatively, or in addition, the secretome contains MCP-1 and IL-6 in a weight ratio of approximately 3:1 to approximately 4:1. Alternatively, or in addition, the secretome contains MCP-1 and IL-8 in a weight ratio of approximately 4:1 to approximately 6:1. Alternatively, or in addition, secretome contains MCP-1 to VEGF in a weight ratio of approximately 4:1 to approximately 6:1. Alternatively, or in addition, secretome contains MCP-1 to VEGF in a weight ratio of approximately 7:1 to approximately 9:1. Alternatively, or in addition, secretome contains MCP-1 and PDGF-AA, with MCP-1 and PDGF-AA present in a weight ratio of approximately 3:1 to approximately 5:1. Alternatively, or in addition, secretome contains MCP-1 and PDGF-AA, with MCP-1 and PDGF-AA present in a weight ratio of approximately 6:1 to approximately 9:1.Alternatively, or in addition, the secretome contains MCP-1 and PDGF-AA, which are present in a weight ratio of approximately 30:1 to approximately 60:1. In some cases, the ratio of MCP-1 to any one of the following proteins—CXCL2, IL-6, IL-8, and VEGF—is in the range of approximately 30:1 to approximately 60:1. Alternatively, or in addition, the secretome contains MCP-1, CXCL2, IL-6, IL-8, and VEGF proteins. In some cases, the secretome contains MCP-1, CXCL2 (GRO), and one, two, three, four, or all of the following proteins: IL-8, MCP-3, IL-6, G-CSF, and VEGF.

[0049]

[0051] A secretome comprising MCP-1 and CXCL2 in a weight ratio of approximately 2:1 to approximately 3:1 is provided herein. In some cases, the secretome further comprises IL-8, and the weight ratio of MCP-1 to IL-8 in the secretome or composition is in the range of approximately 10:1 to approximately 6:1, and / or the weight ratio of CXCL2 to IL-8 in the secretome or composition is in the range of approximately 3:1 to approximately 4:1. In some cases, the secretome The secretome further comprises MCP-3 and / or CXCL2, with the weight ratio of MCP-1 to MCP-3 in the secretome or composition being in the range of about 10:1 to about 30:1, and / or the weight ratio of CXCL2 to MCP-3 in the secretome or composition being in the range of about 5:1 to about 15:1. In some cases, the secretome further comprises IL-6 and / or CXCL2, with the weight ratio of MCP-1 to IL-6 in the secretome or composition being in the range of about 30:1 to about 50:1, and / or the weight ratio of CXCL2 to IL-6 in the secretome or composition being in the range of about 10:1 to about 20:1. In some cases, the secretome further comprises G-CSF and CXCL2, with the weight ratio of MCP-1 to G-CSF in the secretome or composition ranging from about 30:1 to about 50:1, and / or the weight ratio of CXCL2 to G-CSF in the secretome or composition ranging from about 10:1 to about 20:1. In some cases, the secretome further comprises CXCL2 and VEGF, with the weight ratio of MCP-1 to VEGF in the secretome or composition ranging from about 30:1 to about 50:1, and the weight ratio of CXCL2 to VEGF in the secretome or composition ranging from about 10:1 to about 20:1. In some cases, the composition further comprises one or more proteins from among IP-10, eotaxin, Flt-3L, GM-CSF, MIP-1a, MIP-1b, IL-1a, IL-1RA, IL-4, IL-7, IL-10, IL-12P40, IL-13, IL-15, IL-17A, CCL5 (RANTES), MDC, MCP-3, IL-12P70, IFN-alpha (IFN-α), interferon receptor (IFNR), PDGF-AB / BB, or EGF.

[0050]

[0052] In some cases, the composition contains two or more proteins from among CXCL2(GRO)CCL5(RANTES), MCP-1, MCP-3, MDC, fractalkine, IL-6, IL-8, PGDF-AA, PDGF-AB / BB, VEGF, EGF, and G-CSF. In some cases, the composition contains CXCL2(GRO) and CCL5(RANTES) in a weight ratio of approximately 1:1 to approximately 1:2, or approximately 1:1 to approximately 1:4. In some cases, the composition contains CXCL2 and MCP-1 in a weight ratio of approximately 3:1 to approximately 1:3, approximately 3:1 to approximately 1:2, or approximately 1:1 to approximately 1:3. In some cases, the composition contains CXCL2 and PDGF-AA in a weight ratio of approximately 2:1 to approximately 5:1. In some cases, the composition contains CXCL2 and PDGF-AB / BB in a weight ratio of approximately 3:1 to approximately 4:1, or approximately 40:1 to approximately 60:1. In some cases, the composition contains CXCL2 and IL-6 in a weight ratio of approximately 8:1 to approximately 10:1, or approximately 20:1 to approximately 30:1. In some cases, the composition contains CXCL2 and IL-8 in a weight ratio of approximately 10:1 to approximately 15:1, or approximately 4:1 to approximately 5:1. In some cases, the composition contains CXCL2 and MDC in a weight ratio of approximately 15:1 to approximately 50:1. In some cases, the composition contains CXCL2 and fractalkine in a weight ratio of approximately 20:1 to approximately 50:1. In some cases, the composition contains CXCL2 and MCP-3 in a weight ratio of approximately 10:1 to approximately 30:1, or approximately 3:1 to approximately 5:1. In some cases, the composition contains CXCL2 and VEGF in a weight ratio of approximately 10:1 to approximately 20:1, approximately 10:1 to approximately 40:1, or approximately 20:1 to approximately 30:1. In some cases, the composition contains CXCL2 and EGF in a weight ratio of approximately 30:1 to approximately 60:1. In some cases, the composition contains CXCL2 and G-CSF in a weight ratio of approximately 10:1 to approximately 40:1, or approximately 20:1 to approximately 30:1. In some cases, the composition further contains IL-10, MCP-3, eotaxin, MIP-1a, MIP-1b, IL-4, IL-1RA, IL-10, IL-12P40, IL-15, IL-1a, IL-17A, FGF-2 (bFGF), Flt-3L, G-CSF, and GM-CSF.

[0051]

[0053] In some cases, the compositions disclosed herein contain hydrophilic surfactants. In some cases, the compositions contain vitamins. In some cases, the compositions contain hydrophobic surfactants. In some cases, the compositions contain fatty acid molecules. In some cases, The composition contains linoleic acid. In some cases, the composition contains collagen. In some cases, the composition contains hyaluronic acid.

[0052]

[0054] In some cases, the composition does not contain serum, antibiotics, or any combination thereof. In some cases, the composition does not contain steroids, cholesterol, choline chloride, hypoxanthine sodium salt, thymidine, putrescine dihydrochloride, ferric nitrate, L-glutamine, or any combination thereof. In some cases, the composition does not contain coloring additives.

[0053]

[0055] In some cases, the compositions disclosed herein may be sterile. In some cases, the compositions may contain one or more commensal microorganisms or cells. One or more microorganisms or cells may be viruses, bacteria, eukaryotic cells, or any combination thereof. In some cases, one or more microorganisms or cells may not be pathogenic. In some cases, the compositions may contain one or more bacteria at concentrations of less than 10 colony-forming units (CFU) / gram (g), less than 50 CFU / g, less than 100 CFU / g, less than 150 CFU / g, less than 200 CFU / g, less than 300 CFU / g, less than 400 CFU / g, less than 500 CFU / g, less than 600 CFU / g, less than 700 CFU / g, less than 800 CFU / g, less than 900 CFU / g, or less than 1000 CFU / g. In some cases, the composition may contain bacteria at concentrations of approximately 10 CFU / g to approximately 1000 CFU / g, approximately 10 CFU / g to approximately 50 CFU / g, approximately 20 CFU / g to approximately 100 CFU / g, approximately 50 CFU / g to approximately 200 CFU / g, approximately 100 CFU / g to approximately 250 CFU / g, approximately 200 CFU / g to approximately 500 CFU / g, approximately 500 CFU / g to approximately 700 CFU / g, or approximately 600 CFU / g to approximately 1000 CFU / g. In some cases, the composition may contain Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, species of the genus Pseudomonas, and Klebsiella pneumoniae. Or, any combination thereof may be substantially absent, or they may not be present at all.

[0054]

[0056] In some cases, the compositions disclosed herein may not contain heavy metals, such as lead, bithionol, chlorofluorocarbon propellants, nitrosamines, chloroform, salicylanilide halogens, hexachlorophene, mercury compounds, 1,4-dioxane, methylene chloride, prohibited bovine-derived materials, sunscreen compounds, vinyl chloride, zirconium-containing complexes, or any combination thereof. In some cases, prohibited bovine-derived materials may include the brain, skull, eyes, trigeminal ganglion, spinal cord, vertebral column, dorsal root ganglion, tonsils, terminal ileum of the small intestine, or any combination thereof. In some cases, the compositions may contain lead at a level of less than 10 ppm (parts per million).

[0055]

[0057] In some cases, the compositions described herein do not contain color additives. In some cases, the compositions may contain color additives. In some cases, the compositions may contain incidental components, such as color additives, in non-significant levels, for example, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or less than 0.1%. In some cases, incidental components do not have to have a technical / structural, functional, or any combination thereof effect in the composition; for example, incidental components are not active ingredients.

[0056]

[0058] In some cases, the compositions disclosed herein may comprise alpha hydroxy acids, beta hydroxy acids, diethanolamine (DEA), talc, or any combination thereof. In some cases, the beta hydroxy acid may comprise salicylic acid, beta hydroxybutanoic acid, tropic acid, tretocanic acid, their salts, or any combination thereof. In some cases, the diethanolamine may comprise cocamide DEA, cocamide monoethanolamine (MEA), cetyl phosphate DEA, oleth-3 phosphate DEA, lauramine The composition may contain DEA, linoleamide MEA, myristamide DEA, oleamide DEA, stearamide MEA, lauryl sulfate TEA, triethanolamine, its salts, or any combination thereof. In some cases, the composition contains fragrances, parabens, phthalates, alcohols, or any combination thereof in amounts, for example, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or less than 0.1%. In some cases, the fragrance may be a fragrance, cologne, aftershave, essential oil, or any combination thereof. In some cases, the composition does not contain fragrances, parabens, phthalates, alcohols, or any combination thereof.

[0057]

[0059] In some cases, the excipients disclosed herein may include water, glycerol, saline solution, vegetable oils (e.g., seed oils), fruit oils, flower extracts, mineral oils, synthetic oils, sugar compounds, silicates, calcium salts, magnesium salts, sodium chloride, potassium chloride, lactic acid, starch, sugar alcohols, cellulose, activated carbon, glycerin, butter, amino acids, paraffin, honey, wax, beeswax, agar, calcium carbonate, citric acid, tartaric acid, stearic acid, xanthan gum, benzoic acid, polyethylene glycol, silicone, its derivatives, its salts, or any combination thereof. In some cases, the compositions disclosed herein may include fillers, binders, disintegrants, coatings, adsorbents, anti-adhesion agents, lubricants, flow enhancers, antioxidants, surfactants, flavoring and deodorizing agents, solvents, buffers, chelating agents, viscosity modifiers, surfactants, wetting agents, or any combination thereof.

[0058]

[0060] In some cases, the compositions disclosed herein may include a dermal filler. In some cases, the dermal filler may be hyaluronic acid, calcium hydroxyl apatite, poly-L-lactic acid, polymethyl methacrylate, autologous fat, BOTOX®, or any combination thereof.

[0059]

[0061] In some cases, the compositions disclosed herein may contain preservatives. In some cases, the preservatives may be organic / natural compounds, synthetic compounds, or any combination thereof. In some cases, the preservatives may be antimicrobial agents, antibacterial agents, antifungal agents, antiviral agents, preservatives, surfactants, or any combination thereof. In some cases, the preservatives may be parabens, formaldehyde-releasing agents, isothiazolinones, phenoxyethanol, organic acids, quaternary ammonium compounds, or any combination thereof.

[0060]

[0062] In some cases, the compositions disclosed herein may contain ingredients suitable for use as cosmetics. In some cases, the compositions may be safe under the indicated or customary use conditions. In some cases, packaged products containing the compositions may be appropriately labeled, and the use of the ingredients will not otherwise cause the cosmetics to fail to meet legal standards or to be mislabeled. In some cases, conditions that would cause a product to fail to meet legal standards include any toxic or harmful substance that could harm the user; unclean, spoiled or decomposed substance; cosmetics that may have been prepared, packaged or held under unsanitary conditions; containers that may contain toxic or harmful substances that could make the contents harmful to health; or any combination thereof.

[0061]

[0063] In some cases, the secretomes disclosed herein may be stem cell-derived. In some cases, the stem cells are not embryonic stem cells, mesenchymal stem cells, adult stem cells, induced pluripotent stem cells, fetal cells, or any combination thereof. In some cases, the stem cells may be of animal origin, for example, human origin. In some cases, the stem cells are in They may be grown in vitro, for example, in cell culture. In some cases, the secretome may contain proteins or fragments of them that do not contain intact cells.

[0062]

[0064] In some cases, the secretome may include monocyte chemotactic protein (MCP-1), MCP-3, granule cell colony-stimulating factor (G-CSF), CXC motif chemokine ligand 2 (CXCL2), CXCL2 (GRO), interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), PDGF-AA, PDGF-BB, PDGF-AB, any derivative thereof, any biologically active fragment thereof, or any combination thereof.

[0063]

[0065] In some cases, the composition contains protein (e.g., MCP-1) in amounts less than 1 nanogram / milliliter (ng / ml), less than 2 ng / ml, less than 3 ng / ml, less than 4 ng / ml, less than 5 ng / ml, less than 6 ng / ml, less than 7 ng / ml, less than 8 ng / ml, less than 9 ng / ml, less than 10 ng / ml, less than 11 ng / ml, less than 12 ng / ml, less than 13 ng / ml, less than 14 ng / ml, less than 15 ng / ml, less than 16 ng / ml, less than 17 ng / ml, less than 18 ng / ml, less than 19 ng / ml, less than 20 ng / ml, less than 21 ng / ml, less than 22 ng / ml, It may be included at concentrations of less than 23 ng / ml, less than 24 ng / ml, less than 25 ng / ml, less than 30 ng / ml, less than 35 ng / ml, less than 40 ng / ml, less than 45 ng / ml, less than 50 ng / ml, less than 60 ng / ml, less than 70 ng / ml, less than 80 ng / ml, less than 90 ng / ml, less than 100 ng / ml, less than 200 ng / ml, less than 300 ng / ml, less than 400 ng / ml, less than 500 ng / ml, less than 600 ng / ml, less than 700 ng / ml, less than 800 ng / ml, less than 900 ng / ml, less than 1000 ng / ml, or less than 10000 ng / ml. In some cases, the direction may include MCP-1 at concentrations of approximately 1 ng / ml to 100 ng / ml, approximately 10 ng / ml to 200 ng / ml, approximately 10 ng / ml to 400 ng / ml, approximately 50 ng / ml to 300 ng / ml, approximately 100 ng / ml to 200 ng / ml, approximately 150 ng / ml to 400 ng / ml, approximately 200 ng / ml to 600 ng / ml, approximately 400 ng / ml to 700 ng / ml, approximately 500 ng / ml to 900 ng / ml, approximately 600 ng / ml to 1000 ng / ml, approximately 900 ng / ml to 1500 ng / ml, or approximately 1000 ng / ml to 10000 ng / ml.

[0064]

[0066] In some cases, secretome may constitute at least 0.01%, 0.1%, 1%, 1.25%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% of the composition. In some cases, secretome may constitute approximately 0.01% to 0.1%, approximately 0.01% to 1%, approximately 1% to 2%, approximately 1% to 5%, approximately 3% to 8%, approximately 5% to 10%, approximately 10% to 20%, approximately 20% to 40%, approximately 30% to 50%, approximately 50% to 75%, approximately 60% to 90%, approximately 75% to 95%, or approximately 80% to 99% of the composition.

[0065]

[0067] In some cases, the compositions described herein may include exosomes, liposomes, nanoparticles, or any combination thereof. In some cases, liposomes may be in the form of nanoparticles. In some cases, nanoparticles may include liposomes. In some cases, exosomes, liposomes, nanoparticles, or any combination thereof may include secretomes, phospholipids, proteins, hydrophilic surfactants, hydrophilic surfactants, vitamins, inactive components, or any combination thereof. Examples of liposomes, but not limited to these, include monolayer liposomes, multilayer liposomes, archaeosomes, noosomes, novasomes, cryptosomes, emulsomes, besosomes, nanoliposomes, nanoemulsions, or any derivatives thereof, or any combination thereof. Examples of nanoparticles, but not limited to these, include biopolymer nanoparticles, alginate nanoparticles, xanthan gum nanoparticles, cellulose nanoparticles, and lipid nanoparticles. Examples include children, dendrimers, polymer micelles, polyplexed inorganic nanoparticles, nanocrystals, metal nanoparticles, quantum dots, protein nanoparticles, polysaccharide nanoparticles, any derivatives thereof, or any combination thereof.

[0066]

[0068] In some cases, nanoparticles have a diameter of less than 1 nanometer (nm), less than 2 nm, less than 3 nm, less than 4 nm, less than 5 nm, less than 6 nm, less than 7 nm, less than 8 nm, less than 9 nm, less than 10 nm, less than 11 nm, less than 12 nm, less than 13 nm, less than 14 nm, less than 15 nm, less than 16 nm, less than 17 nm, less than 18 nm, less than 19 nm, less than 20 nm, less than 21 nm, less than 22 nm, less than 23 nm, less than 24 nm, 2 It is also acceptable for wavelengths less than 5nm, less than 26nm, less than 27nm, less than 28nm, less than 29nm, less than 30nm, less than 35nm, less than 40nm, less than 45nm, less than 50nm, less than 60nm, less than 70nm, less than 80nm, less than 90nm, less than 100nm, less than 200nm, less than 300nm, less than 400nm, less than 500nm, less than 600nm, less than 700nm, less than 800nm, less than 900nm, or less than 1000nm. In some cases, nanoparticles have a diameter greater than 1 nanometer (nm), greater than 2 nm, greater than 3 nm, greater than 4 nm, greater than 5 nm, greater than 6 nm, greater than 7 nm, greater than 8 nm, greater than 9 nm, greater than 10 nm, greater than 11 nm, greater than 12 nm, greater than 13 nm, greater than 14 nm, greater than 15 nm, greater than 16 nm, greater than 17 nm, greater than 18 nm, greater than 19 nm, greater than 20 nm, greater than 21 nm, greater than 22 nm, greater than 23 nm, greater than 24 nm The wavelengths may be greater than 25nm, greater than 26nm, greater than 27nm, greater than 28nm, greater than 29nm, greater than 30nm, greater than 35nm, greater than 40nm, greater than 45nm, greater than 50nm, greater than 60nm, greater than 70nm, greater than 80nm, greater than 90nm, greater than 100nm, greater than 200nm, greater than 300nm, greater than 400nm, greater than 500nm, greater than 600nm, greater than 700nm, greater than 800nm, greater than 900nm, or greater than 1000nm.In some cases, the nanoparticles may have an average particle size with a diameter of approximately 1 nm to 100 nm, 10 nm to 200 nm, 10 nm to 400 nm, 50 nm to 300 nm, 100 nm to 200 nm, 150 nm to 400 nm, 200 nm to 600 nm, 400 nm to 700 nm, 500 nm to 900 nm, 600 nm to 1000 nm, or 700 nm to 1500 nm.

[0067]

[0069] In some cases, the compositions described herein may contain hydrophobic surfactants, fatty acid molecules, ceramides, phospholipids, linoleic acid, or any combination thereof. In some cases, the fatty acids may be omega-6 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, linoleic acid, stearic acid, oleic acid, lauric acid, myristic acid, palmitic acid, alpha-linolenic acid, gamma-dihomo-gamma-linolenic acid, arachidonic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, hydroxy fatty acids, prostaglandins, any derivatives thereof, or any combination thereof. In some cases, the fatty acids, phospholipids, or any combination thereof may be contained in oil. In some cases, the oil may be sunflower seed oil, safflower oil, evening primrose oil, borage oil, olive oil, argan oil, jojoba oil, tea tree oil, rosemary oil, castor oil, peppermint oil, linseed oil, menhaden fish oil, hemp oil, shea butter, grapeseed oil, poppy seed oil, almond oil, apricot kernel oil, sesame oil, wheat germ oil, avocado oil, turtle oil, mink oil, animal oil, vegetable oil, coconut oil, essential oil, or any combination thereof. In some cases, the phospholipid may be saturated phospholipid, unsaturated phospholipid, monoacyl phospholipid, or any combination thereof. In some cases, the phospholipid may contain liposomes, exosomes, or any combination thereof. In some cases, the phospholipid may be phosphatidic acid (phosphatidic acid salt), phosphatidylethanolamine (cephalin). The steroid may be phosphatidylcholine (lecithin), phosphatidylserine, phosphoinositide, phosphatidylinositol, phosphatidylinositol phosphate, phosphatidylinositol bisphosphate, phosphatidylinositol triphosphate, ceramide phosphorylcholine (sphingomyelin), ceramide phosphorylethanolamine (sphingomyelin), ceramide phosphoryl lipid, any derivative thereof, or any combination thereof. In some cases, the composition may be substantially free of steroids. In some cases, the composition may be substantially free of cholesterol. For example, the steroid may be alclomethasone, amcinonide, beclomethasone, betamethasone, clobetasol, crocoltolone, desonide, diflorasone, fluocinolone, hydrocortisone, halcinonide, mometasone, triamcinolone, any derivative thereof, or any combination thereof.

[0068]

[0070] In some cases, the compositions described herein may contain hydrophilic surfactants, vitamins, or any combination thereof. In some cases, the vitamins may include vitamin B5, provitamin B5, vitamin A, vitamin B3, vitamin C, vitamin E, derivatives thereof, salts thereof, or any combination thereof. In some cases, the compositions may contain collagen. In some cases, the collagen may include type I, type II, type III, type IV, type V, type VI, type VII, derivatives thereof, or any combination thereof. In some cases, the compositions may be substantially free of serum, antibiotics, or any combination thereof.

[0069] Method for preparing a composition

[0071] In some embodiments, compositions formulated as pharmaceutical compositions are disclosed herein. In some embodiments, compositions formulated as medicinal cosmetic compositions are disclosed herein. In some cases, the compositions can be prepared by mixing a secretome and, optionally, one or more activators and pharmaceutically acceptable excipients. In some cases, the excipients include one or more of cellulose, disodium hydrogen phosphate, hydroxypropylcellulose, hypromellose, lactose, mannitol, or sodium lauryl sulfate. In some cases, the compositions further include glyceryl monostearate 40-50, hydroxypropylcellulose, hypromellose, magnesium stearate, methacrylate copolymer type C, polysorbate 80, sugar spheres, talc, or triethyl citrate. In some cases, the compositions further include carnauba wax, crospovidone, diacetylated monoglycerides, ethylcellulose, hydroxypropylcellulose, hypromellose phthalate, magnesium stearate, mannitol, sodium hydroxide, sodium stearyl fumarate, talc, titanium dioxide, or yellow ferric oxide. In some cases, the composition further comprises calcium stearate, crospovidone, hydroxypropyl methylcellulose, iron oxide, mannitol, methacrylate copolymer, polysorbate 80, povidone, propylene glycol, sodium carbonate, sodium lauryl sulfate, titanium dioxide, and triethyl citrate. Examples of carriers for the composition include, for example, any biocompatible polymer, generally biocompatible, in the form of a liquid, matrix, or beads, such as polystirex, polypropylene, polyethylene, polarilex, polylactic acid (PLA), polyglycolic acid (PGA), and / or polyglycolic acid polylactic acid (PGLA).

[0070]

[0072] In some cases, the pH values ​​of the liquid compositions disclosed herein are about 2.5 to about 5.0, 6.0 to about 8.0, about 5.0 to about 9.0, about 4.0 to about 10.0, about 7.0 to about 8.0, about 7.0 to about 9.0, about 7.0 to about 10.0, about 6.0 to about 7.0, about 5.0 to about 7.0, or about 4.0 to about 7.0. The pH of the liquid composition is about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, or about 12. In some cases, the compositions disclosed herein include a buffer, such as a phosphate buffer.

[0071]

[0073] In some cases, a method for preparing a liquid composition includes blending a mixture containing one or more activators under conditions that minimize the introduction of air. Conditions that minimize, reduce, and / or eliminate the introduction of air and / or bubbles include, alone, in combination, and / or in any order, the following steps: combining, for example, water and a thixotrope with one or more preservatives, colorants, and flavoring agents using a membrane pump; installing a recirculation pipe below the surface of the liquid; adding the liquid along the side of a container that holds the liquid; sprinkling beads (e.g., one or more beads containing one or more activators) on the surface of the liquid, if necessary; mixing the solution in the absence of one or more paddles scraping the container; mixing the solution using a propeller mixer; or mixing the solution using a propeller mixer at a rate that reduces or minimizes cavity formation, or any combination of two or more of these steps. In another embodiment, a method for preparing a liquid composition comprises the step of blending a mixture of one or more controlled-release beads / particles with one or more activators on a carrier in a solution having a low ion concentration and a thixotrope, under conditions that minimize the introduction of bubbles.

[0072]

[0074] In some cases, the liquid compositions disclosed herein are suspensions comprising beads (e.g., microbeads), wherein some of the beads have an immediate release profile and others have a controlled release profile. In some cases, one or more beads comprise enteric coatings, resin coatings, lacquer coatings, pH-sensitive coatings, biodegradable polymer matrices, water-soluble matrices, ionic matrices, or any combination thereof. In some cases, one or more beads comprise cellulose, ethylcellulose, methylcellulose, propylcellulose, methoxypropylcellulose, cellulose nitrate, poly(vinyl alcohol), poly(vinyl chloride), polystyrene, polyethylene, polypropylene, poly(ethylene-co-vinyl acetate), poly(hydroxybutyric acid), poly(hydroxyvaleric acid-co-hydroxybutyric acid), poly(lactic acid), poly(glycolic acid), poly(lactic acid-co-glycolic acid), poly(epsilon-caprolactone), poly(epsilon-caprolactone-co-DL-lactic acid), poly(maleic anhydride), polyamide, gelatin The material comprises one or more polymers selected from chitosan, collagen, poly(hydroxyalkyl)-L-glutamine, poly(gamma-ethyl-L-glutamate-co-glutamic acid), poly(L-leucine-co-L-aspartic acid), poly(proline-co-glutamic acid), poly(alkyl 2-cyanoacrylate), polyurethane, poly(methyl methacrylate), poly(methyl methacrylate-co-methacrylic acid), and poly(methacrylate-co-hydroxypropyl methacrylate), polystyrene, polistirex, polarilex, salts thereof, and any combination thereof.

[0073]

[0075] In some cases, the compositions disclosed herein are in the form of unit dosage forms or dosage forms for multiple doses. A unit dosage form, as used herein, refers to a physically distinct unit, individually packaged and suitable for administration to human or non-human animal subjects. Each unit dose contains a predetermined amount of the active ingredient sufficient to produce the desired therapeutic effect in combination with the necessary pharmaceutically acceptable carrier or excipient. Examples of unit dosage forms, but not limited to, include ampoules, syringes, and individually packaged tablets and capsules. In some cases, a unit dosage form is administered in divided doses or in multiple doses. A dosage form for multiple doses is a plurality of identical unit dosage forms packaged in a single container, which are administered in the form of separate unit dosage forms. Examples, though not limited to these, include vials, bottles of tablets or capsules, or bottles of several pints or gallons. In some cases, the dosage form for multiple doses contains different pharmaceutically active ingredients.

[0074]

[0076] In some embodiments, the compositions disclosed herein may have liposomes, which can be prepared in a variety of ways acceptable to the composition. In some cases, the preparation of liposomes may include drying lipids, dispersing lipids, purifying liposomes, and analyzing the final product. In some cases, liposomes can be prepared by methods including ultrasonic treatment, sonication, French pressure cell, extrusion, membrane extrusion, lipid membrane hydration, or any combination thereof. In some cases, nanoliposomes can be prepared from liposomes by reducing particle size using high-pressure homogenization, ultrasound, or membrane extrusion. In some cases, nanoemulsions can be formed by mixing oil, emulsifier, and water. In some cases, oil-in-water or water-in-oil nanoemulsions may be formed.

[0075]

[0077] In some embodiments, secretome proteins, such as cytokines, chemokines, or any combination thereof, may be present in a free form (soluble), on the surface of an exosome (bound to the surface), encapsulated within an exosome, or in any combination thereof. Exosomes may be included in the composition in the form of liposomes that encapsulate exosomes by encapsulating the exosomes in liposomes. In some cases, exosomes may be in any form as long as they are suitable for use in the composition. In some cases, exosomes can be used without encapsulation in liposomes. In some cases, when exosomes are used in the form of liposome encapsulation, the exosomes may be included in an amount of about 0.1% to about 10.0% by weight, or about 0.1% to about 1.0% by weight, based on the total weight of the liposomes. In some cases, the liposomes that encapsulate the exosomes may be present in amounts of about 0.001% to about 10.0% by weight, about 0.001% to about 1.0% by weight, about 0.01% to about 1.0% by weight, or about 0.01% to about 0.1% by weight, based on the total weight of the entire composition.

[0076]

[0078] In some cases, about 3% by weight of lecithin may be dispersed in an aqueous phase containing about 0.01% by weight of stem cell-derived exosomes (e.g., at about 15 degrees Celsius), and then supercritical carbon dioxide may be used to form a reverse micelle emulsion (water and carbon dioxide of the low-temperature process). In some cases, the reaction can be terminated and the supercritical carbon dioxide phase can be removed by vaporizing the supercritical carbon dioxide under reduced pressure, thereby obtaining a liposome suspension by a low-temperature process that can encapsulate the exosomes. In some cases, the composition can be prepared such that the liposomes that encapsulate the exosomes may be contained in an amount of about 5% by weight based on the total weight of the entire composition.

[0077]

[0079] In some cases, nanoliposomes can be prepared from a precursor solution. In some cases, the precursor solution may be prepared by solubilizing an amphiphilic material in a first amount of non-aqueous solvent suitable for solubilizing the amphiphilic material to form a first mixture. The amphiphilic material may contain phospholipids (PL). The PL may contain one or more of the following phosphatides: phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and phosphatidylinositol (PI). In some cases, PC, PE, PA, and PI are combined. In some cases, a useful PL ratio may be PC:PE:PA:PI in ethanol of approximately 6.5:2.5:0.7:0.3. In some cases, 1g Lamb's PL is solubilized in 5.0 ml to 7.5 ml of ethanol solvent. In some cases, after dissolving the amphiphilic material, a predetermined amount of water may be added to form a turbid suspension. In some cases, the amount of water added may be about 9 kg for about 31 kg of dissolved amphiphilic material, but this may be changed to obtain the desired turbid suspension. In some cases, a second amount of a non-aqueous solvent, such as ethanol, may be added until the turbid suspension becomes single-phase and has optical clarity at room temperature. In some cases, the resulting product may be a precursor solution that can be stored for a long period of time. In some cases, the precursor solution prepared by this method may be stable for at least about 1, 2, 3, 4, 5, 6, 8, or 9 years, regardless of manufacture, arrangement, season, year, and / or lot. In some cases, the precursor solution can be used as a starting material for preparing nanoliposomes and nanoliposome assemblies. In some cases, the precursor solution may be useful for fabricating amphiphilic carrier structures represented as solvent dilution microcarriers (SDMCs). In some cases, the SDMCs may have a diameter of approximately 230 to 412 nm. In some cases, the nanoliposomes may have an average diameter of approximately 1 nm to 20 nm, and the nanoliposome aggregates may have an average diameter of approximately 30 nm to 200 nm.

[0078]

[0080] In some cases, to prepare a carrier for passenger molecules, such as a nanoliposome population, a nanoliposome aggregate, or a mixed population of lysosomes, the precursor solution may be diluted with a suitable solvent or mixed solvent system that is compatible with the solvent system used in the precursor solution. In some cases, this dilution may be performed either before or after the addition of the passenger molecules. The solvent may be selected according to biocompatibility, depending on the end use of the carrier which may require its characteristics. In some cases, the solvent or mixed solvent system used for dilution may be miscible with the solvent in the precursor solution and may be effective in dispersing the carrier. In some cases, the solvent used for dilution may be ethanol. In some cases, dilution may be performed sequentially or in a continuous manner. For example, a first dilution of about 1:10 provides a population of carriers, and further sequential dilutions down to about 1:0.5 provide a series of carrier populations. The size of the carriers in each dilution may be determined by laser light scattering. In some cases, mixed populations of nanoliposomes and larger vesicles can be produced in non-aqueous solvents at lower dilution ratios. A suitable instrument for this purpose may be the ZETASIZER® 1000, manufactured by Malvern Instruments (Worcestershire, United Kingdom). The particle diameters reported herein were determined using the Multimodal Analysis Mode of the ZETASIZER® 1000, with particle size determined by peak intensity. In some cases, particle size can be analyzed using other techniques, and the results may correlate with numerical values ​​obtained using light scattering techniques. In some cases, the addition of the desired passenger molecule may be performed before dilution with a solvent if the passenger molecule is lipophilic or amphiphilic. In some cases, the addition is performed after dilution if the passenger molecule is water-soluble. In some cases, for lipophilic or amphiphilic passenger molecules, the nanoliposome-loaded population can be formed when diluted with a solvent.In some cases, a collection of nanoliposome aggregates or a mixed collection of liposomes can be formed by diluting a nanoliposome-loaded collection in water.

[0079] How to use

[0081] In some embodiments, the compositions disclosed herein require administration of the compositions. Methods comprising the step of administering to a subject (e.g., a human) are disclosed herein. In some cases, the method treats a disease in the subject. In some cases, the method To restore the condition of the target skin.

[0080]

[0082] In some cases, the compositions described herein can be used to treat diseases. In some cases, the compositions described herein can be used to facilitate autocrine, juxtacrine, and paracrine action. In some cases, administration involves injecting the composition, for example, intravenously, intramuscularly, or subcutaneously. In some cases, the composition can be applied directly to the treatment site, for example, as a topical treatment applied to a wound. In some cases, the compositions described herein can be used as prophylactic agents, for example, as prophylactic agents for the aging of tissues or organs. In some cases, the compositions described herein can be used as regenerative medicine agents. In some cases, the compositions described herein can be used for tissue repair to treat various conditions resulting from damage or injury to tissues, organs, or any combination thereof. In some cases, the compositions described herein are used to treat or prevent stroke, alopecia, baldness, cartilage defects, myocardial infarction, hind limb ischemia, spinal cord injury, nerve injury, lung injury, bone defects, subgingival periodontal ligament defects, periodontal disease, skin wounds, brain injury, traumatic brain injury, liver failure, graft-versus-host disease (GVHD), or any combination thereof. In some cases, the compositions described herein can be used to treat chronic diseases. In some cases, the chronic disease may be kidney disease, liver disease, or any combination thereof.

[0081]

[0083] In some embodiments, methods for modulating skin conditions are disclosed herein. In some cases, the methods can be used to treat skin diseases or conditions. In some cases, the diseases or conditions are eczema, rash, psoriasis, acne, rosacea, ichthyosis, vitiligo, urticaria, seborrheic dermatitis, herpes zoster, burns, sunburn, contact dermatitis, wrinkled skin, scarred skin, sagging skin, loss of skin elasticity, dry skin, dull skin, or any combination thereof. In some cases, the methods can reduce the appearance of skin aging, photoaging, or any combination thereof. In some cases, the methods can reduce the appearance of scars. In some cases, the methods can improve wound healing. In some cases, the methods can prevent, reduce, or eliminate bruises, benign growths, age spots, cancerous growths, ulcers, infections, or any combination thereof. In some cases, this method can prevent, reduce, or eliminate skin ridges, wrinkles, or any combination thereof. In some cases, ridges or wrinkles may be crow's feet, laugh lines, frown lines, forehead wrinkles, tear troughs, bunny lines, nasolabial folds, marionette lines, mental creases, necklines, age-related wrinkles, wrinkle lines, fibrous elastica wrinkles, expression lines, gravity folds, dynamic wrinkles, static wrinkles, atrophic wrinkles, atrophic shrunk wrinkles, or any combination thereof. In some cases, this method can prevent, reduce, or eliminate loss of skin volume, elasticity, or any combination thereof. In some cases, this method can prevent, reduce, or eliminate sagging skin, dull skin tone, blemishes, rough skin, dry skin, itchy skin, thinning skin, or any combination thereof.

[0082]

[0084] In some cases, this method can improve or restore skin condition, skin disease, or any combination thereof. In some cases, this method can moisturize, tighten, lift, or rejuvenate the skin. In some cases, this method can restore or maintain healthy, smooth, blemish-free, clear, elastic, or any combination thereof of skin. In some cases, this method can repair, treat, and restore the glycosaminoglycans, dermis, collagen, and elastin of the skin, or any combination thereof. In some cases, the improved health of the skin can be measured by wrinkle severity scale, transepidermal water loss measurement, skin color measurement, skin surface morphometry, viscoelasticity measurement by CUTOMETER®, histological examination, or any combination thereof. Yes, it is possible. In some cases, the improved skin health can be measured by diagnostic imaging, such as magnetic resonance imaging (MRI). In some cases, measurements can be compared before and after administration of the composition. In some cases, measurements can be compared against a standard.

[0083]

[0085] In some cases, the administration of the composition may be topical or cutaneous. In some cases, topical dosage forms may be lotions, solutions, emulsions, pastes, suspensions, tablets, sticks, aerosols (e.g., sprays, puffs, or foams), butters, oils, creams, patches, gels (e.g., hydrogels), milk or emulsion forms, sprays, drips, liquids, powders, solids, ointments, beads, masks, pads (e.g., impregnated pads), sheets, dispersants, microemulsions, or any combination thereof. In some cases, the composition may be applied by pouring, sprinkling, spraying, rubbing, on top of, or otherwise introduced. In some cases, topical administration may be administered directly to the site having the condition. In some cases, patches may include membranes, microneedle patches, single-layer cosmetics in adhesives, multi-layer cosmetics in adhesives, reservoir systems, matrix systems, or any combination thereof. In some cases, the compositions herein may be in the form of wound dressings, bandages (e.g., coated bandages or those covered with other polymers), ointments, creams, lotions, pastes, gels, sprays, or aerosols.

[0084]

[0086] In some cases, the administration of the composition may be by injection. In some cases, the injection may include administering an injector, subcutaneous injection, intradermal injection, dermal injection, intravenous injection, intra-arterial injection, intramuscular injection, intra-orbital injection, intraperitoneal injection, intravenous injection, intraventricular injection, stereotactic injection, or any combination thereof. In some cases, the injection may be administered directly to the site of the condition.

[0085]

[0087] In some cases, the subject may be administered the composition in the absence of supervision. In some cases, the cosmetic may be administered by another person, nurse, clinician, physician, beautician, cosmetologist, medical professional, or any combination thereof.

[0086] Method for preparing therapeutic compositions under hypoxic conditions

[0088] In one aspect, a method for producing one or more proteins of interest from trophoblast cell lines, comprising culturing human trophoblast stem cells with a nutrient medium until confluence is achieved; inducing hypoxia; and isolating one or more proteins of interest from the medium, is provided herein. In some cases, hypoxia is induced over approximately 12 - 48 hours, and in some cases, over approximately 24 hours. Confluence can vary depending on the culture dish being utilized. Non-limiting examples of confluence are from about 3,000 cells / cm to about 9,000 cells / cm 2 ; from about 4,000 cells / cm 2 to about 8,000 cells / cm 2 ; from about 5,000 cells / cm 2 to about 7,000 cells / cm<e000012>; or from about 6,000 cells / cm 2 and may include. The method according to any one of claims 70 - 72, wherein the isolated one or more proteins may be further mixed, as necessary, with one or more pharmaceutically acceptable excipients to prepare a composition.

[0087]

[0089] The methods described are cytokines, growth factors, membrane-bound signaling molecules, cell adhesion molecules, defense proteins, immune proteins, and extracellular matrix proteins, intracellular signaling molecules, metabolite exchange enzymes, protein modification enzymes ( / proteases, protein-binding modulators / protease inhibitors, scaffolds / adaptor proteins, structural proteins, transport proteins or carrier proteins, transmembrane signal receptors ​​One or more proteins may be produced, which may contain the contents or any combination thereof. Secretomes produced from any one of the described methods are useful in one or more of the following processes: biological adhesion / cell adhesion, bioregulation, cell proliferation, cellular component organization or biodevelopment, cellular processes (e.g., cell activation, cell communication, cell cycle processes, cell death, cell growth, cellular component organization, cell development processes, cell differentiation, cellular component morphogenesis, cellular metabolic processes, cellular responses to stimuli, export from cells, microtubule-based processes, cell activation, cell communication, cell cycle processes, cell death, cell growth, cellular component organization, cellular development processes (e.g., cell differentiation or cellular component morphogenesis), cellular metabolic processes, cellular responses to stimuli, export from cells, microtubule-based processes, movement of cells or intracellular components, cell motility, neuronal projection guidance, myelin formation, signal transduction, etc. ), developmental processes (e.g., development of anatomical structures, formation of anatomical structures involved in morphogenesis, morphogenesis of anatomical structures, cell development processes, growth and development, etc.), proliferation, immune system processes (e.g., immune effector processes, immune responses, immune system development, leukocyte activation, leukocyte migration, etc.), localization (e.g., cell localization, establishment of localization, cell localization, macromolecule localization, etc.), mobility (e.g., cell motility, chemotaxis, etc.), metabolic processes (e.g., biosynthesis processes, catabolic processes, cellular metabolic processes, hormone metabolic processes, nitrogen compound metabolic processes, etc.), processes of multiple organisms / responses to other organisms, multicellular biological processes (e.g., coagulation, cytokine production, digestion, multicellular organism development, system processes, etc.), responses to stimuli (e.g., cellular responses to stimuli, immune responses, etc.), signal transduction (e.g., intercellular signal transduction, signal conversion, etc.).

[0088]

[0090] Secretomes produced by any one of the methods described are useful in one or more of the following pathways: Alzheimer's disease-amyloid secretase pathway; Alzheimer's disease-presenilin pathway; angiogenesis; apoptosis signaling pathways; Slit / Robo-mediated axonal guidance; Netrin-mediated axonal guidance; blood coagulation; CCKR signaling map; cadherin signaling pathway; endothelin signaling pathway; FAS signaling pathway; gonadotropin-releasing hormone receptor pathway; inflammation mediated by chemokine and cytokine signaling pathways; insulin / IGF pathway-MAPKK / MAPK cascade; insulin / IGF pathway-PKB signaling cascade; interleukin signaling pathway; PDGF signaling pathway; plasminogen activation cascade; T cell activation; TGF-beta signaling pathway; Toll receptor signaling pathway; Wnt signaling pathway; P53 pathway, etc.

[0089]

[0091] In one example, the method produces one or more proteins containing chemokine (CC motif) ligand 13 (CCL13), CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXC motif chemokine ligand 1 (CXCL1), CXCL11, CXCL12, CXCL14, CXCL15, Pf4, or any combination thereof. In another example, the method produces one or more proteins containing secreted phosphoprotein 1 (SPP1), DKK1, serpine family E member 1 (SERPINE1), FLT1, follistatin-like protein 3 (FSTL3), matrine 3 (MATN3), pregnancy-associated plasma protein A (PAPPA), growth and differentiation factor 15 (GDF15), human growth factor (HGF), insulin-like growth factor-binding protein 3 (IGFBP3), or any combination thereof. In another example, the method produces one or more proteins containing FST, Nidogen 1 (NID1), MET (MET oncogene, receptor tyrosine kinase), TGFβI, Follistatin-like 1 (FSTL1), Nidogen 2 (NID2), Cysteine-rich motor neuron 1 (CRIM1), Platelet-derived growth factor subunit B (PDGFB), or any combination thereof. In yet another example, the method produces one or more proteins containing CXCL12, Galectin 1 (LGALS1), ADAMTS-like 1 (ADAMTSL1), or any combination thereof. In yet another example, the method contains FAP, IGFBP3, or any combination thereof. In another example, the method produces one or more proteins, including CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, platelet factor 4 (PF4), or a combination thereof. In yet another example, the method produces one or more proteins, including colony-stimulating factor 1 (CSF1), growth and differentiation factor 15 (GDF15), interferon lambda 1 (IFNL1), interferon lambda 2 (IFNL2), interleukin 21 (IL21), IL6, macrophage migration inhibitor (MIF), nicotinamide phosphoribosyltransferase (NAMPT), SPP1, TGFβ1, TIMP metallopeptidase inhibitor 1 (TIMP1), or a combination thereof. In another example, the method produces one or more proteins including CSF1, CXCL12, DKK1, GDF15, HGF, IL6, PDGFB, TGFB1, TIMP1, or a combination thereof. In yet another example, the method produces one or more proteins including ANG, CSTB, NAP1L4, Toll-like receptor 3 (TLR3), or a combination thereof. In yet another example, the method produces one or more proteins including ADAMTSL1, DCN, furin, lumican (LUM), matrine 3 (MATN3), matrix metalloproteinase 1 (MMP1), NID1, NID2, PDGFB, periostin (POSTN), pentraxin 3 (PTX3), SERPINE, SPP1, TGFβI, thrombospondin 1 (THBS1), TIMP1, TIMP2, CCN1, LUM, MATN3, NID1, NID2, POSTN, or a combination thereof.

[0090]

[0092] In another example, the method produces one or more proteins including ANG, beta-2-microglobulin (B2M), BCL10, CCL13, CCL20, CCL25, CCL28, CCL4, CD99, CLU, CSF1, CXCL1, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, F11 receptor (F11R), Fas cell surface death receptor (FAS), IFNL1, IFNL2, IL21, IL6, IL7R, LGALS3, MIF, osteoclast-associated Ig-like receptor (OSCAR), PF4, PTX3, SERPINE1, sialic acid-binding Ig-like lectin 9 (SIGLEC9), THBS1, TLR3, TNF receptor superfamily member 21 (TNFRSF21), or a combination thereof. In another example, the method produces one or more proteins including CCL13, CCL13, CCL20, CCL25, CCL4, CCL5, CCL7, CCL8, CSF1, CXCL1, CXCL12, F11R, IGFBP4, IL6, MIF, nucleoporin 85 (NUP85), PF4, PTX3, semaphorin 7A (SEMA7A), SPP1, THBS1, TNFRSF1A, or a combination thereof. The method according to any one of claims 70 to 73, wherein one or more proteins include ANG, CCL13, CCL20, CCL25, CCL26, CCL8, CLU, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, LGALS3, PF4, ANG, B2M, CCL20, KLK3, TLR3, TNFRSF1A, CCL4, IFNL1, IFNL2, IL21, IL6, TLR3, or a combination thereof. In another example, the method produces one or more proteins including ANG, B2M, CCL20, KLK3, TLR3, TNFRSF1A, or any combination thereof. In another example, the method produces one or more proteins including CCL4, IFNL1, IFNL2, IL21, IL6, TLR3, or any combination thereof. In another example, this method produces one or more proteins including DCN, POSTN, syndecan-4 (SDC4), granulin (GRN), PAPPA, TIMP1, or a combination thereof.In another example, the method produces one or more proteins including angiopoietin 1 (ANGPT1), Fms-related receptor tyrosine kinase 1 (FLT1), MET, cystatin C (CST3), Dickkopf-related protein 3 (DKK3), retinol-binding protein 4 (RBP4), basidine (BSG), or a combination thereof. In yet another example, the method contains ANG, decorin (DCN), and baculovirus IAP repeat. The method produces one or more proteins including 2 (BIRC2), platelet-derived growth factor subunit B (PDGFB), or a combination thereof. In another example, the method produces one or more proteins including the tissue inhibitor of metalloproteinase 4 (TIMP4), CRIM1, Unc-5 Netrin receptor C (UNC5C), the tissue inhibitor of metalloproteinase 2 (TIMP2), or a combination thereof. In yet another example, the method produces one or more proteins including Dickkopf-related protein 1 (DKK1), follistatin (FST), transforming growth factor β1 (TGFβ1), FLT1, DKK3, cell communication network factor 1 (CCN1), or a combination thereof.

[0091]

[0093] In another example, the method produces one or more proteins containing NAP1L4, SPP1, ANGPT1, FST, MET, CTSB, FSTL1, LGALS1, tripeptidyl peptidase 1 (TPP1), OSCAR, CCN1, IGFBP3, TGFβ1, B2M, IL7R, carboxylesterase 1 (CES1), colony-stimulating factor 1 (CSF1), or any combination thereof. In another example, the method produces one or more proteins containing SPP1, OSCAR, CCN1, IGFBP3, or any combination thereof. In another example, the method produces one or more proteins containing CSF1, MET, CCN1, TGFβ1, or LGALS1. In another example, the method produces one or more proteins containing B2M, IL7R, or a combination thereof. In another example, the method produces one or more proteins containing CTSB, TPP1, CES1, or any combination thereof. In another example, the method produces one or more proteins containing SIGLEC9, POSTN, TGFβI, or a combination thereof. In yet another example, the method produces one or more proteins containing OSCAR, B2M, or a combination thereof. In yet another example, the method produces one or more proteins containing LGALS3, LGALS1, or a combination thereof. In yet another example, the method produces one or more proteins containing XC motif chemokine ligand 1 (XCL1), TGFβ1, CCL5, CCL20, CCL28, CCL4, CXCL5, ANGPTL4, PDGFB, CCL13, CCL8, ANGPTI, CCL25, CXCL11, CCL7, PF4, GDF15, CCL26, SEMA7A, SPP1, CXCL1, or a combination thereof. In another example, the method produces one or more proteins including XCL1, CCL5, CCL20, CCL28, CCL4, CXCL5, CCL13, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SPP1, CXCL1, or a combination thereof. In yet another example, the method produces one or more proteins including TGFβI, PDGFB, GDF15, or a combination thereof.In another example, this method produces one or more proteins, including SEMA7A.

[0092]

[0094] In another example, the method produces one or more proteins including CES1, FAS, MIF, NAMPT, SPP1, or a combination thereof. In yet another example, the method produces one or more proteins including fibroblast-activating protein alpha (FAP), legmine (LGMN), HGF, cathepsin B (CTSB), TPP1, kallikrein-associated peptidase 3 (KLK3), furin, MMP1, or a combination thereof. In yet another example, the method produces one or more proteins including IGFBP3, TIMP4, FSTL1, BIRC2, FST, SERPINE1, TIMP1, IGFBP2, FSTL3, IGFBP4, TIMP2, or a combination thereof. In yet another example, the method produces one or more proteins including BSG, NUP85, or low-density lipoprotein receptor (LDLR). In another example, the method produces one or more proteins including albumin (ALB), tripeptidyl peptidase 1 (TPP1), LDLR, retinol-binding protein 4 (RBP4), transferrin (TF), or a combination thereof. In yet another example, the method produces UNC5C, TLR3 The method produces one or more proteins, including plasminogen activator, urokinase receptor (PLAUR), glycoprotein Ib platelet subunit alpha (GP1BA), SDC4, thrombomodulin (THBD), IL7R, TF, or a combination thereof. In another example, the method produces one or more proteins, including SIGLEC9, CD99, TNF receptor superfamily member 21 (TNFRSF21), GP1BA, BSG, POSTN, TGFβI, or a combination thereof. In another example, this method produces one or more proteins including XCL1, IGFBP3, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, FST, SERPINE1, GP1BA, PDGFB, F11R, CCL13, TIMP1, NID1, CCL8, NUP85, IGFBP6, THBS1, CCL25, IGFBP2, FSTL3, IGFBP4, KLK3, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, TIMP2, SEMA7A, furin, DKK1, INFRSF10C, CXCL1, or a combination thereof. In another example, this method produces one or more proteins, including TGFβ1, TNFRSF21, PDGFB, or a combination thereof.

[0093]

[0095] In another example, the method produces one or more proteins including UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof. In yet another example, the method produces one or more proteins including TNFRSF21, GP1BA, or a combination thereof. In yet another example, the method produces one or more proteins including XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof. In another example, the method produces one or more proteins containing BIRC2, BCL10, LGALS3, TNFRSF21, INFRSF10C, or a combination thereof. In another example, the method produces one or more proteins containing SEMA7A. In another example, the method produces one or more proteins containing UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof. In another example, the method produces one or more proteins containing UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof. In another example, the method produces one or more proteins containing UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof. In another example, this method produces one or more proteins including UNC5C, BSG, SEMA7A, or a combination thereof.In another example, this method produces one or more proteins including XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, CCL26, TIMP2, SEMA7A, furin, or a combination thereof.

[0094]

[0096] In another example, this method produces one or more proteins including XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof. In this example, the method produces one or more proteins containing TNFRSF21. In another example, the method produces one or more proteins containing TNFRSF21, GP1BA, or a combination thereof. In yet another example, the method produces one or more proteins containing XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof. In another example, the method produces one or more proteins containing BIRC2, BCL10, LGALS3, TNFRSF21, INFRSF10C, or a combination thereof. In another example, the method produces one or more proteins containing UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof. In another example, the method produces one or more proteins containing UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof. In another example, the method produces one or more proteins containing UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof. In another example, the method produces one or more proteins containing UNC5C, BSG, SEMA7A, or a combination thereof. In another example, this method produces one or more proteins including XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, CCL26, TIMP2, SEMA7A, furin, or a combination thereof.In another example, this method produces one or more proteins including XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof. In another example, this method produces one or more proteins including XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof.

[0095]

[0097] In another example, the method produces one or more proteins containing UNC5C, BSG, SEMA7A, or a combination thereof. In yet another example, the method produces one or more proteins containing TNFRSF21. In yet another example, the method produces one or more proteins containing XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof. In another example, the method produces one or more proteins containing UNC5C, FSTL1, PTX3, TNFRSF21, FST, MET, FUR, BSG, THBS1, FLT1, FSTL3, SEMA7A, or a combination thereof. In yet another example, the method produces one or more proteins containing UNC5C, FSTL1, PTX3, TNFRSF21, FST, MET, FUR, BSG, THBS1, FLT1, FSTL3, SEMA7A, or a combination thereof. In yet another example, the method produces one or more proteins containing THBS1.

[0096]

[0098] In another example, the method produces one or more proteins containing UNC5C, PTX3, BSG, THBS1, SEMA7A, or a combination thereof. In yet another example, the method produces one or more proteins containing UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof. In yet another example, the method produces one or more proteins containing XCL1, CCL5, CCL20, CCL4, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, PTX3, CCL13, IFNL1, CCL8, FLT1, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof. In yet another example, the method produces one or more proteins containing IFNL1, SEMA7A, or a combination thereof. In another example, the method produces one or more proteins containing XCL1, CCL5, CCL20, CCL4, BCL10, CXCL5, TNFRSF21, PTX3, CCL13, IFNL1, CCL8, FLT1, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof. In another example, the method produces one or more proteins containing FLT1. In another example, the method produces one or more proteins containing TNFRSF21. In another example, the method produces one or more proteins containing XCL1, CCL5, CCL20, CCL4, BCL10, CD99, LGALS3, CXCL5, CCL13, CCL8, CXCL11, CCL7, PF4, CCL26, CXCL1, or a combination thereof. In another example, the method produces one or more proteins containing NUP85, GPC1, or a combination thereof. In yet another example, the method produces one or more proteins containing ALB, LGALS3, TNFRSF21, MET, F11R, NUP85, or a combination thereof.In another example, the method produces one or more proteins including XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof. In yet another example, the method produces one or more proteins including TNFRSF21, NUP85, GPC1, or a combination thereof.

[0097]

[0099] In another example, the method produces one or more proteins containing XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, or a combination thereof. In yet another example, the method produces one or more proteins containing CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof. In yet another example, the method produces one or more proteins containing XCL1, UNC5C, CCL5, CCL20, CCL4, LGALS3, CXCL5, CCL13, BSG, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof. In another example, the method produces one or more proteins containing TGFβ1, FSTL1, BCL10, FST, NUP85, FSTL3, GDF15, or a combination thereof. In yet another example, the method produces one or more proteins containing TIMP4, LGMN, CED1, TIMP1, CTSB, TIMP2, MMP1, or a combination thereof. In yet another example, the method produces one or more proteins containing XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, CCL26, TIMP2, SEMA7A, furin, or a combination thereof. In yet another example, the method produces one or more proteins containing furin. In another example, this method is used for XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CC In another example, the method produces one or more proteins containing L8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, or a combination thereof. In yet another example, the method produces one or more proteins containing CCL26, TIMP2, SEMA7A, furin, or a combination thereof. In yet another example, the method produces one or more proteins containing XCL1, CCL5, CCL20, CCL4, CXCL5, PTX3, CCL13, IFNL1, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, CXCL1, or a combination thereof.

[0098]

[0100] In another example, this method involves using one or more proteins, including GP1BA. In another example, the method produces one or more proteins comprising TNFRSF21, SEMA7A, or a combination thereof. In yet another example, the method produces one or more proteins comprising UNC5C, FSTL1, TNFRSF21, FST, MET, BSG, THBS1, FLT1, FSTL3, SEMA7A, or a combination thereof. In yet another example, the method produces one or more proteins comprising TNFRSF21, FUR, KLK3, or a combination thereof. In another example, this method produces one or more proteins including XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof. In another example, the method produces one or more proteins including XCL1, CCL5, CCL20, CCL4, BCL10, CXCL5, TNFRSF21, PTX3, CCL13, IFNL1, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof. In yet another example, the method produces one or more proteins including NID1, DKK1, DKK3, or a combination thereof. In another example, the method produces one or more proteins including XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof. In yet another example, the method produces one or more proteins including FSTL1, furin, MMP1, or a combination thereof.In another example, the method produces one or more proteins including PDGFB, ANGPT1, TF, or a combination thereof. In yet another example, the method produces one or more proteins including BIRC2, FAS, TNFRSF1A, INFRSF10C, or a combination thereof.

[0099]

[0101] In another example, this method involves one or more proteins containing CXCL12. In another example, the method produces one or more proteins containing UNC5C. In another example, the method produces one or more proteins containing SERPINE1, PLAUR, GP1BA, THBD, KLK3, TF, or a combination thereof. In another example, the method produces one or more proteins containing BIRC2, SERPINE1, CLU, CXCL1, or a combination thereof. In another example, the method produces one or more proteins containing FSTL1. In another example, the method produces one or more proteins containing FAS. In another example, the method produces one or more proteins containing TGFβ1, macrophage migration inhibitory factor (MIF), follistatin (FST), insulin (INS), or a combination thereof. In another example, the method produces one or more proteins containing IL6, CCL5, CCL20, CCL4, CCL13, CCL8, CCL7, PF4, CCL26, or a combination thereof. The method produces proteins. In another example, the method produces one or more proteins including insulin (INS). In another example, the method produces one or more proteins including IL6, IL21, or a combination thereof. In another example, the method produces one or more proteins including platelet-derived growth factor beta (PDGFβ). In another example, the method produces one or more proteins including SEREPIN1, PLAUR, MMP1, or a combination thereof. In another example, the method produces one or more proteins including β2-microglobulin (B2M).

[0100]

[0102] In another example, this method includes TGFβ1, GDF15, or a combination thereof. In another example, the method produces one or more proteins. In yet another example, the method produces one or more proteins containing Toll-like receptor 3 (TLR3). In yet another example, the method produces one or more proteins containing follistatin-like receptor 1 (FSTL1). In yet another example, the method produces one or more proteins containing IGFBP3, SEREPINE1, FAS, THBS1, or a combination thereof. In yet another example, the method produces one or more proteins containing f11R.

[0101] Exemplary compositions and their therapeutic or in vitro / ex vivo use

[0103] The following compositions are provided herein: a) a secretome in an amount of about 0.1 w / w% or more and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL15, PF4, or any combination thereof. In one example, the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, 11, 12, 13, or 14 of CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL15, and PF4. In another example, the secretome includes CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL15, and PF4. A method for inducing chemokine activity in a subject is provided herein, comprising administering one of such compositions to a subject requiring induction of chemokine activity, wherein the composition induces chemokine activity in the subject. A use of one of such compositions for treating a subject requiring induction of chemokine activity is provided herein, wherein the composition induces chemokine activity in the subject. A use of one of such compositions for manufacturing a pharmacopoeia for treating a subject requiring induction of chemokine activity is provided herein, wherein the composition induces chemokine activity in the subject.

[0102]

[0104] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients are provided herein, wherein the secretome comprises one or more of SPP1, DKK1, SERPINE1, FLT1, FSTL3, MATN3, PAPPA, GDF15, HGF, and IGFBP3, or any combination thereof. In one example, the secretome comprises one, two, three, four, five, six, seven, eight, or nine of SPP1, DKK1, SERPINE1, FLT1, FSTL3, MATN3, PAPPA, GDF15, HGF, and IGFBP3. In another example, the secretome comprises SPP1, DKK1, SERPINE1, FLT1, FSTL3, MATN3, PAPPA, GDF15, HGF, and IGFBP3. Any of these compositions are useful for inducing biased expression in the placenta. A method is provided herein comprising the step of administering one of such compositions to a subject requiring administration of the composition, wherein the composition induces chemokine activity in the subject. The use of one of such compositions for treating a subject requiring treatment is evident herein. Provided herein in detail. Uses of any of such compositions for manufacturing pharmaceuticals for treating subjects requiring treatment are provided herein.

[0103]

[0105] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of FST, NID1, MET, TGFBI, FSTL1, NID2, CRIM1, and PDGFB, or any combination thereof. In one example, the secretome comprises one, two, three, four, five, six, or seven of FST, NID1, MET, TGFBI, FSTL1, NID2, CRIM1, and PDGFB. In another example, the secretome comprises FST, NID1, MET, TGFBI, FSTL1, NID2, CRIM1, and PDGFB. Any of these compositions is useful for inducing broad expression in the placenta. A method comprising the step of administering any of these compositions to a subject requiring administration of the composition is provided herein. Use of any of these compositions for treating a subject requiring it is provided herein. Use of any of these compositions for manufacturing a pharmacopoeia for treating a subject requiring it is provided herein.

[0104]

[0106] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of CXCL12, LGALS1, and ADAMTSL1, or any combination thereof. In one example, the secretome comprises one or two of CXCL12, LGALS1, and ADAMTSL1. In another example, the secretome comprises CXCL12, LGALS1, and ADAMTSL1. Any of these compositions is useful for inducing broad endometrial expression. A method comprising the step of administering any of these compositions to a subject requiring administration of the composition is provided herein. Use of any of these compositions for treating a subject requiring treatment is provided herein. Use of any of these compositions for manufacturing a pharmacopoeia for treating a subject requiring treatment is provided herein.

[0105]

[0107] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of FAP, IGFBP3, or a combination thereof, are provided herein. In one example, the secretome comprises FAP or IGFBP3. In another example, the secretome comprises FAP and IGFBP3. Any of such compositions is useful for inducing biased endometrial expression. A method is provided herein comprising the step of administering any of such compositions to a subject requiring administration of the composition. The use of any of such compositions for treating a subject requiring treatment is provided herein. The use of any of such compositions for manufacturing a pharmacopoeia for treating a subject requiring treatment is provided herein.

[0106]

[0108] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients are provided herein, wherein the secretome comprises one or more of CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, PF4, or combinations thereof. In one example, the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, 11, 12, 13, or 14 of CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, and PF4. In another example, secretomes include CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, and CC. The composition comprises L7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, and PF4. Any of these compositions is useful for inducing chemokine activity. A method is provided herein comprising the step of administering any of these compositions to a subject requiring administration of the composition. The use of any of these compositions is provided herein for treating a subject requiring treatment who has a disease or condition treatable with chemokines. The use of any of these compositions is provided herein for manufacturing a pharmacopoeia for treating a subject requiring treatment who has a disease or condition treatable with chemokines.

[0107]

[0109] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of the following: CSF1, GDF15, IFNL1, IFNL2, IL21, IL6, MIF, NAMPT, SPP1, TGFB1, TIMP1, or combinations thereof. In one example, the secretome comprises one, two, three, four, five, six, seven, eight, nine, or ten of the following: CSF1, GDF15, IFNL1, IFNL2, IL21, IL6, MIF, NAMPT, SPP1, TGFB1, and TIMP1. In another example, the secretome comprises CSF1, GDF15, IFNL1, IFNL2, IL21, IL6, MIF, NAMPT, SPP1, TGFB1, and TIMP1. Any of these compositions are useful for inducing cytokine activity. A method comprising the step of administering any of these compositions to a subject requiring administration of the composition is provided herein. The use of any of such compositions for treating subjects requiring treatment who have a disease or condition that can be treated with cytokines is provided herein. The use of any of such compositions for manufacturing a pharmacopoeia for treating subjects requiring treatment who have a disease or condition that can be treated with cytokines is also provided herein.

[0108]

[0110] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of the following: CSF1, CXCL12, DKK1, GDF15, HGF, IL6, PDGFB, TGFB1, TIMP1, or combinations thereof. In one example, the secretome comprises one, two, three, four, five, six, seven, or eight of the following: CSF1, CXCL12, DKK1, GDF15, HGF, IL6, PDGFB, TGFB1, and TIMP1. In another example, the secretome comprises CSF1, CXCL12, DKK1, GDF15, HGF, IL6, PDGFB, TGFB1, and TIMP1. Any of these compositions are useful for inducing growth. A method comprising the step of administering any of these compositions to a subject requiring administration of the composition is provided herein. The use of any of these compositions for treating a subject requiring treatment having a disease or condition treatable with growth factors is provided herein. The use of any such composition is provided herein for manufacturing a pharmaceutical for treating a subject requiring treatment, which has a disease or condition that can be treated with growth factors.

[0109]

[0111] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of ANG, CSTB, NAP1L4, TLR3, or a combination thereof, are provided herein. In one example, the secretome comprises one, two, or three of ANG, CSTB, NAP1L4, and TLR3. In another example, the secretome comprises ANG, CSTB, NAP1L4, and TLR3. Any of such compositions is useful for inducing RNA binding activity. A method for inducing RNA binding activity in a subject requiring induction of RNA binding activity is provided, comprising administering any of such compositions to the subject. Methods for including such compositions are provided herein. Use of any of such compositions for inducing RNA binding activity in subjects requiring induction of RNA binding activity is provided herein. Use of any of such compositions for producing pharmaceuticals for inducing RNA binding activity in subjects requiring induction of RNA binding activity is provided herein.

[0110]

[0112] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of ADAMTSL1, DCN, furin, LUM, MATN3, MMP1, NID1, NID2, PDGFB, POSTN, PTX3, SERPINE, SPP1, TGFβI, THBS1, TIMP1, TIMP2, CCN1, LUM, MATN3, NID1, NID2, POSTN, or a combination thereof, are provided herein. In one example, the secretome includes one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve In another example, the secretome comprises ADAMTSL1, DCN, Furin, LUM, MATN3, MMP1, NID1, NID2, PDGFB, POSTN, PTX3, SERPINE, SPP1, TGFβI, THBS1, TIMP1, TIMP2, CCN1, LUM, MATN3, NID1, NID2, and POSTN. Any of these compositions is useful for inducing extracellular matrix organization. A method for inducing extracellular matrix organization in a subject requiring induction of extracellular matrix organization is provided herein, comprising the step of administering any of these compositions to a subject requiring induction of extracellular matrix organization. The use of any of these compositions for inducing extracellular matrix organization in a subject requiring induction of extracellular matrix organization is provided herein. The use of any of these compositions for manufacturing a pharmacopoeia for inducing extracellular matrix organization in a subject requiring induction of extracellular matrix organization is provided herein.

[0111]

[0113] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of ANG, B2M, BCL10, CCL13, CCL20, CCL25, CCL28, CCL4, CD99, CLU, CSF1, CXCL1, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, F11R, FAS, IFNL1, IFNL2, IL21, IL6, IL7R, LGALS3, MIF, OSCAR, PF4, PTX3, SERPINE1, SIGLEC9, THBS1, TLR3, TNFRSF21, or combinations thereof, are provided herein. In one example, the secretome includes ANG, B2M, BCL10, CCL13, CCL20, CCL25, CCL28, CCL4, CD99, CLU, CSF1, CXCL1, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, F11R, FAS, IFNL1, IFNL2, IL21, IL6, IL7R, LGALS3, MIF, OS Includes one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen In another example, secretome includes ANG, B2M, BCL10, CCL13, CCL20, CCL25, CCL28, CCL4, CD99, CLU, CSF1, CXCL1, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, F11R, FAS, IFNL1, IFNL2, IL21, IL6, IL7R, LGALS3, MIF, OSCAR, PF4, PTX3, SERPINE1, SIGLEC9, THBS1, TLR3, and TNFRSF21. Any of these is useful for inducing an immune response. A method for inducing an immune response in a subject requiring induction of an immune response is provided herein, comprising the step of administering any of such compositions to a subject requiring induction of an immune response. The use of any of such compositions for inducing an immune response in a subject requiring induction of an immune response is provided herein. The use of any of such compositions for manufacturing a pharmacopoeia for inducing an immune response in a subject requiring induction of an immune response is provided herein.

[0112]

[0114] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of the following: CCL13, CCL13, CCL20, CCL25, CCL4, CCL5, CCL7, CCL8, CSF1, CXCL1, CXCL12, F11R, IGFBP4, IL6, MIF, NUP85, PF4, PTX3, SEMA7A, SPP1, THBS1, TNFRSF1A, or combinations thereof, are provided herein. In one example, the secretome includes one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve In another example, secretome comprises CCL13, CCL13, CCL20, CCL25, CCL4, CCL5, CCL7, CCL8, CSF1, CXCL1, CXCL12, F11R, IGFBP4, IL6, MIF, NUP85, PF4, PTX3, SEMA7A, SPP1, THBS1, and TNFRSF1A. Any of these compositions is intended for use in treating inflammation. A method for treating inflammation in a subject requiring treatment of inflammation is provided herein, comprising administering any of these compositions to the subject. The use of any of these compositions for treating inflammation in a subject requiring treatment of inflammation is provided herein. The use of any of these compositions for manufacturing a pharmacopoeia for treating inflammation in a subject requiring treatment of inflammation is provided herein.

[0113]

[0115] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. The following compositions containing excipients are provided herein, wherein the secretome comprises one or more of the following, or a combination thereof: ANG, CCL13, CCL20, CCL25, CCL26, CCL8, CLU, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, LGALS3, PF4, ANG, B2M, CCL20, KLK3, TLR3, TNFRSF1A, CCL4, IFNL1, IFNL2, IL21, IL6, TLR3. In one example, the secretome includes one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve In another example, the secretome comprises ANG, CCL13, CCL20, CCL25, CCL26, CCL8, CLU, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, LGALS3, PF4, ANG, B2M, CCL20, KLK3, TLR3, TNFRSF1A, CCL4, IFNL1, IFNL2, IL21, IL6, and TLR3. Any of these compositions may exhibit antimicrobial activity. In one example, the secretome comprises one or more of ANG, B2M, CCL20, KLK3, TLR3, TNFRSF1A, or any combination thereof. In another example, the secretome comprises ANG, B2M, CCL20, KLK 3 comprises TLR3 and TNFRSF1A. Any of such compositions may exhibit antibacterial activity. In one example, the secretome comprises one or more of CCL4, IFNL1, IFNL2, IL21, IL6, and TLR3, or any combination thereof. In another example, the secretome comprises CCL4, IFNL1, IFNL2, IL21, IL6, and TLR3. Any of such compositions may exhibit antiviral activity. Any of such compositions may be intended for use in treating microbial infections. A method for treating a microbial infection in a subject requiring treatment of a microbial infection is provided herein, comprising the step of administering any of such compositions to a subject requiring such administration. The use of any of such compositions for treating a microbial infection in a subject requiring treatment of a microbial infection is provided herein. The use of any of such compositions for manufacturing a medicament for treating a microbial infection in a subject requiring treatment of a microbial infection is provided herein.

[0114]

[0116] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of DCN, POSTN, SDC4, GRN, PAPPA, TIMP1, or a combination thereof. In one example, the secretome comprises one, two, three, four, or five of DCN, POSTN, SDC4, GRN, PAPPA, and TIMP1. In another example, the secretome comprises DCN, POSTN, SDC4, GRN, PAPPA, and TIMP1. Such secretomes are useful for wound healing. Methods for wound healing in subjects requiring wound healing are provided herein, comprising the step of administering one of such compositions to subjects requiring wound healing. Use of any of such compositions for wound healing in subjects requiring wound healing is provided herein. Use of any of such compositions for manufacturing a medicament for wound healing in subjects requiring wound healing is provided herein.

[0115]

[0117] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of ANGPT1, FLT1, MET, CST3, DKK3, RBP4, and BSG, or a combination thereof. In one example, the secretome comprises one, two, three, four, five, or six of ANGPT1, FLT1, MET, CST3, DKK3, RBP4, and BSG. In another example, the secretome comprises ANGPT1, FLT1, MET, CST3, DKK3, RBP4, and BSG. Such secretomes are useful for inducing embryogenesis. Methods for inducing embryogenesis in subjects requiring induction of embryogenesis are provided herein, comprising the step of administering one of such compositions to a subject requiring induction of embryogenesis. Use of one of such compositions for inducing embryogenesis in subjects requiring induction of embryogenesis is provided herein. The use of any of such compositions for manufacturing a pharmaceutical for inducing embryogenesis in subjects requiring the induction of embryogenesis is provided herein.

[0116]

[0118] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of ANG, DCN, BIRC2, PDGFB, or a combination thereof. In one example, the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelfth, twelfth, and PDGFB, and one or fourteen of ANG, DCN, BIRC2, and PDGFB. In another example, the secretome comprises ANG, DCN, BIRC2, and PDGFB. Such secretomes are useful for inducing placental development. Methods for inducing placental development in subjects requiring induction of placental development are also provided herein, comprising the step of administering one of such compositions to a subject requiring induction of placental development. The use of any of such compositions for the purpose of is provided herein. The use of any of such compositions for the purpose of manufacturing a pharmaceutical for inducing placental development in subjects requiring induction of placental development is provided herein.

[0117]

[0119] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of TIMP4, CRIM1, UNC5C, TIMP2, or a combination thereof. In one example, the secretome comprises one, two, or three of TIMP4, CRIM1, UNC5C, and TIMP2. In another example, the secretome comprises TIMP4, CRIM1, UNC5C, and TIMP2. Such secretomes are useful for inducing central nervous system (CNS) development. Methods for inducing CNS development in subjects requiring CNS development are provided herein, comprising the step of administering one of such compositions to subjects requiring CNS development induction. Use of any of such compositions for inducing CNS development in subjects requiring CNS development is provided herein. Use of any of such compositions for manufacturing a medicament for inducing CNS development in subjects requiring CNS development is provided herein.

[0118]

[0120] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of DKK1, FST, TGFB1, FLT1, DKK3, and CCN1, or a combination thereof. In one example, the secretome comprises one, two, three, four, or five of DKK1, FST, TGFB1, FLT1, DKK3, and CCN1. In another example, the secretome comprises DKK1, FST, TGFB1, FLT1, DKK3, and CCN1. Such secretomes are useful for inducing morphogenesis. Methods for inducing morphogenesis in subjects requiring morphogenesis induction are provided herein, comprising the step of administering one of such compositions to subjects requiring morphogenesis induction. Use of any of such compositions for inducing morphogenesis in subjects requiring morphogenesis induction is provided herein. Use of any of such compositions for manufacturing a pharmacopoeia for inducing morphogenesis in subjects requiring morphogenesis induction is provided herein.

[0119]

[0121] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising an excipient is provided herein, wherein the secretome comprises one or more of NAP1L4, SPP1, ANGPT1, FST, MET, CTSB, FSTL1, LGALS1, TPP1, OSCAR, CCN1, IGFBP3, TGFB1, B2M, IL7R, CES1, and CSF1, or any combination thereof. The composition comprises one, two, three, four, five, six, seven, eight, nine, ten, 11, 12, 13, 14, 15, or 16 of NAP1L4, SPP1, ANGPT1, FST, MET, CTSB, FSTL1, LGALS1, TPP1, OSCAR, CCN1, IGFBP3, TGFB1, B2M, IL7R, CES1, and CSF1. In another example, the secretome includes NAP1L4, SPP1, ANGPT1, FST, MET, CTSB, FSTL1, LGALS1, TPP1, OSCAR, CCN1, IGFBP3, TGFB1, B2M, IL7R, CES1, and CSF1. Such a secretome is useful for inducing the differentiation of stem cells. In one example, the secretome includes one or more of SPP1, OSCAR, CCN1, and IGFBP3, or any combination thereof. In another example, the secretome includes SPP1, OSCAR, CCN1, and IGFBP3. Such a secretome is useful for inducing the differentiation of stem cells into osteoblasts. In one example, the secretome includes CSF1. Such a secretome is useful for inducing the differentiation of stem cells into osteoclasts or macrophages. In one example, the secretome contains B2M, IL7R, or a combination thereof. In another example, the secretome contains B2M and IL7R. Such secretomes are useful for inducing the differentiation of stem cells into T cells. In one example, the secretome contains one or more of CTSB, TPP1, and CES1, or any combination thereof. In another example, the secretome contains CTSB, TPP1, and CES1. Such secretomes are useful for inducing the differentiation of stem cells into epithelial cells.

[0120]

[0122] In one example, the secretome includes MET. Such a secretome This is useful for inducing the differentiation of stem cells into neurons. In one example, the secretome contains CCN1. Such a secretome is useful for inducing the differentiation of stem cells into chondrocytes. In one example, the secretome contains TGFβ1. Such a secretome is useful for inducing the differentiation of stem cells into chondrocytes. In one example, the secretome contains LGALS1. Such a secretome is useful for inducing the differentiation of stem cells into myofiform cells. A method for inducing cell differentiation in vitro, ex vivo, or in vivo in subjects requiring induction of cell differentiation is provided herein, comprising administering any of such compositions. The use of any of such compositions for inducing cell differentiation in vitro, ex vivo, or in vivo in subjects requiring induction of cell differentiation is provided herein. Uses of any of such compositions for manufacturing pharmaceuticals for inducing vivo or in vivo cell differentiation are provided herein.

[0121]

[0123] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of SIGLEC9, POSTN, and TGFβI, or a combination thereof. In one example, the secretome comprises one or two of SIGLEC9, POSTN, and TGFβI. In another example, the secretome comprises SIGLEC9, POSTN, and TGFβI. Methods for inducing or promoting cell adhesion in subjects requiring induction or promotion of cell adhesion are provided herein, comprising the step of administering one of such compositions to subjects requiring induction or promotion of cell adhesion. Uses of any of such compositions for inducing or promoting cell adhesion in subjects requiring induction or promotion of cell adhesion, or for manufacturing a pharmacopoeia for inducing or promoting cell adhesion in subjects requiring induction or promotion of cell adhesion are provided herein.

[0122]

[0124] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of OSCAR, B2M, or a combination thereof. In one example, the secretome comprises OSCAR or B2M. In another example, the secretome comprises OSCAR and B2M. Methods for improving or enhancing immunity in subjects requiring improved or enhanced immunity are provided herein, comprising the step of administering one of such compositions to subjects requiring improved or enhanced immunity. Uses of any of such compositions for improving or enhancing immunity in subjects requiring improved or enhanced immunity, or for manufacturing a pharmacopoeia for improving or enhancing immunity in subjects requiring improved or enhanced immunity, are provided herein.

[0123]

[0125] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients are provided herein, wherein the secretome comprises one or more of LGALS3, LGALS1, or a combination thereof. In one example, the secretome comprises LGALS3 or LGALS1. In another example, Cretome comprises LGALS3 and LGALS1. A method for inducing or enhancing the extracellular matrix in a subject requiring induction or enhancement of the extracellular matrix is ​​provided herein, comprising the step of administering one of such compositions to a subject requiring induction or enhancement of the extracellular matrix. The use of one of such compositions for inducing or enhancing the extracellular matrix in a subject requiring induction or enhancement of the extracellular matrix, or for manufacturing a pharmacopoeia for inducing or enhancing the extracellular matrix in a subject requiring induction or enhancement of the extracellular matrix, is also provided herein.

[0124]

[0126] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. The following compositions containing excipients are provided herein, wherein the secretome comprises one or more of XCL1, TGFβ1, CCL5, CCL20, CCL28, CCL4, CXCL5, ANGPTL4, PDGFB, CCL13, CCL8, ANGPTI, CCL25, CXCL11, CCL7, PF4, GDF15, CCL26, SEMA7A, SPP1, and CXCL1, or a combination thereof. In one example, the secretome includes one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve In another example, the secretome includes XCL1, TGFβ1, CCL5, CCL20, CCL28, CCL4, CXCL5, ANGPTL4, PDGFB, CCL13, CCL8, ANGPTI, CCL25, CXCL11, CCL7, PF4, GDF15, CCL26, SEMA7A, SPP1, and CXCL1. In yet another example, the secretome includes cytokine activity, and the secretome includes XCL1, CCL5, CCL20, CCL28, CCL4, CXCL5, CCL13, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SPP1, CXCL1, or a combination thereof. In another example, the secretome includes cytokine activity, and the secretome includes XCL1, CCL5, CCL20, CCL28, CCL4, CXCL5, CCL13, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SPP1, and CXCL1. In another example, the secretome includes growth factor activity, and the secretome includes TGFβI, PDGFB, GDF15, or a combination thereof. In another example, the secretome includes growth factor activity, and the secretome includes TGFβI, PDGFB, and GDF15. In another example, the secretome includes a signaling molecule, and the secretome includes SEMA7A.A method for inducing or enhancing intracellular signaling in subjects requiring induction or enhancement of intracellular signaling is provided herein, comprising the step of administering one of such compositions to subjects requiring induction or enhancement of intracellular signaling. The use of one of such compositions for inducing or enhancing intracellular signaling in subjects requiring induction or enhancement of intracellular signaling, or for producing a pharmaceutical for inducing or enhancing intracellular signaling in subjects requiring induction or enhancement of intracellular signaling, is also provided herein.

[0125]

[0127] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of CES1, FAS, MIF, NAMPT, SPP1, or a combination thereof. In one example, the secretome comprises one, two, three, or four of CES1, FAS, MIF, NAMPT, and SPP1. In another example, the secretome comprises CES1, FAS, MIF, NAMPT, and SPP1. Methods for inducing or enhancing the activity of metabolite reciprocating enzymes in subjects requiring induction or enhancement of the activity of metabolite reciprocating enzymes, comprising any of such compositions. A method comprising the step of administering to a subject requiring induction or enhancement of the activity of a metabolite reciprocating enzyme is provided herein. The use of any such composition is provided herein for inducing or enhancing the activity of a metabolite reciprocating enzyme in a subject requiring induction or enhancement of the activity of a metabolite reciprocating enzyme, or for producing a pharmacopoeia for inducing or enhancing the activity of a metabolite reciprocating enzyme in a subject requiring induction or enhancement of the activity of a metabolite reciprocating enzyme.

[0126]

[0128] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of FAP, LGMN, HGF, CTSB, TPP1, KLK3, furin, and MMP1, or a combination thereof. In one example, the secretome comprises one, two, three, four, five, six, or seven of FAP, LGMN, HGF, CTSB, TPP1, KLK3, furin, and MMP1. In another example, the secretome comprises FAP, LGMN, HGF, CTSB, TPP1, KLK3, furin, and MMP1. Methods for inducing or enhancing the activity of a protease in a subject requiring induction or enhancement of the activity of a protease are also provided herein, comprising the step of administering one of such compositions to a subject requiring induction or enhancement of the activity of a protease. The use of any such composition is provided herein for inducing or enhancing the activity of a protein-modifying enzyme / protease in a subject requiring induction or enhancement of the activity of a protein-modifying enzyme / protease, or for producing a pharmaceutical for inducing or enhancing the activity of a protein-modifying enzyme / protease in a subject requiring induction or enhancement of the activity of a protein-modifying enzyme / protease.

[0127]

[0129] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients are provided herein, wherein the secretome comprises one or more of IGFBP3, TIMP4, FSTL1, BIRC2, FST, SERPINE1, TIMP1, IGFBP2, FSTL3, IGFBP4, and TIMP2, or a combination thereof. In one example, the secretome comprises one, two, three, four, five, six, seven, eight, nine, or ten of IGFBP3, TIMP4, FSTL1, BIRC2, FST, SERPINE1, TIMP1, IGFBP2, FSTL3, IGFBP4, and TIMP2. In another example, the secretome comprises IGFBP3, TIMP4, FSTL1, BIRC2, FST, SERPINE1, TIMP1, IGFBP2, FSTL3, IGFBP4, and TIMP2. Provided herein are methods for inducing or enhancing the activity of a protein-binding modulator / protease inhibitor in a subject requiring induction or enhancement of the activity of the protein-binding modulator / protease inhibitor, comprising the step of administering one of such compositions to a subject requiring induction or enhancement of the activity of the protein-binding modulator / protease inhibitor. Provided herein are the use of one of such compositions for inducing or enhancing the activity of a protein-binding modulator / protease inhibitor in a subject requiring induction or enhancement of the activity of the protein-binding modulator / protease inhibitor, or for producing a pharmaceutical for inducing or enhancing the activity of a protein-binding modulator / protease inhibitor in a subject requiring induction or enhancement of the activity of the protein-binding modulator / protease inhibitor.

[0128]

[0130] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising an excipient, wherein the secretome comprises BSG, is provided herein. A method for inducing or enhancing the activity of a scaffold / adapter protein in subjects requiring induction or enhancement of the activity of a scaffold / adapter protein. The present invention provides a method comprising the step of administering any of such compositions to a subject requiring induction or enhancement of scaffold / adapter protein activity. The present invention also provides the use of any of such compositions for inducing or enhancing scaffold / adapter protein activity in a subject requiring induction or enhancement of scaffold / adapter protein activity, or for producing a pharmaceutical for inducing or enhancing scaffold / adapter protein activity in a subject requiring induction or enhancement of scaffold / adapter protein activity.

[0129]

[0131] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising an excipient, wherein the secretome comprises NUP85, is provided herein. A method for inducing or enhancing the activity of a structural protein in a subject requiring induction or enhancement of the activity of the structural protein, comprising the step of administering one of such compositions to a subject requiring induction or enhancement of the activity of the structural protein. The use of one of such compositions for inducing or enhancing the activity of a structural protein in a subject requiring induction or enhancement of the activity of the structural protein, or for producing a pharmacopoeia for inducing or enhancing the activity of a structural protein in a subject requiring induction or enhancement of the activity of the structural protein, is provided herein.

[0130]

[0132] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of ALB, TPP1, LDLR, RBP4, and TF, or a combination thereof. In one example, the secretome comprises one, two, three, or four of ALB, TPP1, LDLR, RBP4, and TF. In another example, the secretome comprises LDLR. In yet another example, the secretome comprises ALB, TPP1, LDLR, RBP4, and TF. Methods for inducing or enhancing the activity of transport / carrier proteins in subjects requiring induction or enhancement of transport / carrier protein activity are also provided herein, comprising the step of administering one of such compositions to subjects requiring induction or enhancement of transport / carrier protein activity. The use of any such composition is provided herein for inducing or enhancing the activity of transport / carrier proteins in subjects requiring induction or enhancement of transport / carrier protein activity, or for producing pharmaceuticals for inducing or enhancing the activity of transport / carrier proteins in subjects requiring induction or enhancement of transport / carrier protein activity.

[0131]

[0133] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of UNC5C, TLR3, PLAUR, GP1BA, SDC4, THBD, IL7R, TF, or a combination thereof. In one example, the secretome comprises one, two, three, four, five, six, or seven of UNC5C, TLR3, PLAUR, GP1BA, SDC4, THBD, IL7R, and TF. In another example, the secretome comprises UNC5C, TLR3, PLAUR, GP1BA, SDC4, THBD, IL7R, and TF. Methods for inducing or enhancing transmembrane signaling receptor activity in subjects requiring induction or enhancement of transmembrane signaling receptor activity are also provided herein, comprising the step of administering one of such compositions to subjects requiring induction or enhancement of transmembrane signaling receptor activity. The use of any such composition is provided herein for inducing or enhancing the activity of transmembrane signaling receptors in subjects requiring induction or enhancement of transmembrane signaling receptor activity, or for manufacturing a pharmacopoeia for inducing or enhancing the activity of transmembrane signaling receptors in subjects requiring induction or enhancement of transmembrane signaling receptor activity.

[0132]

[0134] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of SIGLEC9, CD99, TNFRSF21, GP1BA, BSG, POSTN, and TGFβI, or a combination thereof. In one example, the secretome comprises one, two, three, four, five, or six of SIGLEC9, CD99, TNFRSF21, GP1BA, BSG, POSTN, and TGFβI. In another example, the secretome comprises SIGLEC9, CD99, TNFRSF21, GP1BA, BSG, POSTN, and TGFβI. Methods for inducing cell adhesion in subjects requiring induction of cell adhesion are provided herein, comprising the step of administering one of such compositions to subjects requiring induction of cell adhesion. Uses of any of such compositions for inducing cell adhesion in subjects requiring induction of cell adhesion, or for manufacturing a pharmacopoeia for inducing cell adhesion in subjects requiring induction of cell adhesion, are also provided herein.

[0133]

[0135] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. This specification provides compositions comprising excipients, wherein the secretome comprises one or more of the following, or a combination thereof: XCL1, IGFBP3, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, FST, SERPINE1, GP1BA, PDGFB, F11R, CCL13, TIMP1, NID1, CCL8, NUP85, IGFBP6, THBS1, CCL25, IGFBP2, FSTL3, IGFBP4, KLK3, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, TIMP2, SEMA7A, Furin, DKK1, INFRSF10C, CXCL1. In one example, the secretome includes XCL1, IGFBP3, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, FST, SERPINE1, GP1BA, PDGFB, F11R, CCL13, TIMP1, NID1, CCL8, NUP85, IGFBP6, THBS1, CCL25, IGFBP2, FSTL3, IGFBP4, KLK3, CXCL11, and GPC1. , including one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelveIn another example, secretome includes XCL1, IGFBP3, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, FST, SERPINE1, GP1BA, PDGFB, F11R, CCL13, TIMP1, NID1, CCL8, NUP85, IGFBP6, THBS1, CCL25, IGFBP2, FSTL3, IGFBP4, KLK3, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, TIMP2, SEMA7A, Furin, DKK1, INFRSF10C, and CXCL1. A method for inducing bioregulation in a subject requiring induction of bioregulation is provided herein, comprising the step of administering any of such compositions to the subject requiring induction of bioregulation. As used herein, "biomodulation" refers to intercellular communication mediated by substances secreted by cells, such as the secretome and action of hTSCs in regulating systemic inflammation or wound healing. The use of any such composition for inducing biomodulation in subjects requiring the induction of biomodulation, or for manufacturing a medicament for inducing biomodulation in subjects requiring the induction of biomodulation, is provided herein.

[0134]

[0136] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of TGFβ1, TNFRSF21, and PDGFB, or a combination thereof. In one example, the secretome comprises one or two of TGFβ1, TNFRSF21, and PDGFB. In another example, the secretome comprises TGFβ1, TNFRSF21, and PDGFB. Methods for inducing cell proliferation in subjects requiring induction of cell proliferation are provided herein, comprising the step of administering one of such compositions to subjects requiring induction of cell proliferation. Uses of any of such compositions for inducing cell proliferation in subjects requiring induction of cell proliferation, or for manufacturing a pharmacopoeia for inducing cell proliferation in subjects requiring induction of cell proliferation are provided herein.

[0135]

[0137] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises one or more of UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, and MMP1, or a combination thereof. In one example, the secretome comprises one, two, three, four, five, six, or seven of UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, and MMP1. In another example, the secretome comprises UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, and MMP1. Methods for inducing cell organization or biodevelopment in subjects requiring induction of cell organization or biodevelopment are also provided herein, comprising the step of administering one of such compositions to subjects requiring induction of cell organization or biodevelopment. The use of any such composition for inducing cell organization or biodevelopment in subjects requiring induction of cell organization or biodevelopment, or for manufacturing a pharmaceutical for inducing cell organization or biodevelopment in subjects requiring induction of cell organization or biodevelopment, is provided herein.

[0136]

[0138] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising excipients, wherein the secretome comprises a. TNFRSF21, GP1BA, or a combination thereof, in which case the secretome induces cell activation; b. XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11 a. Includes GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof, in which case the secretome induces cell communication; c. Includes BIRC2, in which case the secretome induces cell cycle processes or microtubule-based processes; d. Includes BIRC2, BCL10, LGALS3, TNFRSF21, INFRSF10C, or a combination thereof e. Contains SEMA7A, in which case the secretome induces cell death; f. Contains UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof, in which case the secretome induces cellular component organization; g. UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof h. Including UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof, in which case the secretome induces cell differentiation; i. Including UNC5C, BSG, SEMA7A, or a combination thereof, in which case the secretome induces morphogenesis; j. XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1 , including CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, CCL26, TIMP2, SEMA7A, furin, or a combination thereof, in which case the secretome induces cellular metabolic processes; k.XCL1, IGFBP3, TGFβ1, CCL5, C This includes CL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or any combination thereof, in this case, Compositions are provided herein that include secretomes that induce a cellular response to a stimulus; l. TNFRSF21, in this case the secretome induces export from the cell; m. TNFRSF21, GP1BA, or a combination thereof, in this case the secretome induces cell activation; or n. XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof, in this case the secretome induces cell communication.

[0137]

[0139] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising an excipient, wherein the secretome comprises a. XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof, in which case the secretome induces cell motility; b. UNC5C, BSG, SEMA7A, or a combination thereof, in which case the secretome induces neuronal projection guidance; c. TNFRSF21, in which case the secretome Compositions are provided herein that include, inducing myelin formation; or comprising d.XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof, in which case the secretome induces signal transduction.

[0138]

[0140] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising excipients, wherein the secretome comprises a. UNC5C, FSTL1, PTX3, TNFRSF21, FST, MET, FUR, BSG, THBS1, FLT1, FSTL3, SEMA7A, or a combination thereof, in which case the secretome induces developmental processes; b. UNC5C, FSTL1, PTX3, TNFRSF21, FST, MET, FUR, BSG, THBS1, FLT1, FSTL3, SEMA7A, or a combination thereof, in which case the secretome induces the development of anatomical structures; c. THBS1, in which case Compositions are provided herein that include secretomes that induce anatomical structure formation involved in morphogenesis; d. UNC5C, PTX3, BSG, THBS1, SEMA7A, or a combination thereof, in which case the secretome induces anatomical structure morphogenesis; e. UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof, in which case the secretome induces the process of cell development; or f. SEMA7A, or a combination thereof, in which case the secretome induces proliferation.

[0139]

[0141] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising excipients, wherein the secretome comprises a. IFNL1, SEMA7A, or a combination thereof, in which case the secretome induces an immunoeffector process; b. XCL1, CCL5, CCL20, CCL4, BCL10, CXCL5, TNFRSF21, PTX3, CCL13, IFNL1, CCL8, FLT1, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof, in which case the secretome induces an immunoeffector process. Compositions are provided herein that induce responses; c. FLT1, in which case the secretome induces immune system development; d. TNFRSF21, in which case the secretome induces leukocyte activation; or e. XCL1, CCL5, CCL20, CCL4, BCL10, CD99, LGALS3, CXCL5, CCL13, CCL8, CXCL11, CCL7, PF4, CCL26, CXCL1, or a combination thereof, in which case the secretome induces leukocyte migration.

[0140]

[0142] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising excipients, wherein the secretome comprises a. NUP85, GPC1, or a combination thereof, in which case the secretome induces cell localization; b. ALB, LGALS3, TNFRSF21, MET, F11R, NUP85, or a combination thereof, in which case the secretome induces the establishment of localization; c. XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof, in which case the secretome The secretome induces cell localization; d. TNFRSF21, NUP85, GPC1, or a combination thereof, in which case the secretome induces macromolecule localization; e. XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, or a combination thereof, in which case the secretome induces cell motility; f. CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof; or g. XCL1, UNC5C, CCL5, CCL20, CCL4, LGALS3, CXCL5 Compositions comprising CCL13, BSG, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or combinations thereof, in which case the secretome induces chemotaxis, are provided herein.

[0141]

[0143] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising excipients, wherein the secretome comprises a. TGFβ1, FSTL1, BCL10, FST, NUP85, FSTL3, GDF15, or a combination thereof, in which case the secretome induces a biosynthetic process; b. TIMP4, LGMN, CED1, TIMP1, CTSB, TIMP2, MMP1, or a combination thereof, in which case the secretome induces a catabolic process; c. XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, CCL26, TI Compositions comprising MP2, SEMA7A, furin, or a combination thereof, in which case the secretome induces cellular metabolic processes; d. furin, in which case the secretome induces hormonal metabolic processes; e. XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, or a combination thereof, in which case the secretome induces nitrogen compound metabolic processes; or compositions comprising CCL26, TIMP2, SEMA7A, furin, or a combination thereof are provided herein.

[0142]

[0144] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises XCL1, CCL5, CCL20, CCL4, CXCL5, PTX3, CCL13, IFNL1, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, CXCL1, or a combination thereof, are provided herein.

[0143]

[0145] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. Compositions comprising excipients, wherein the secretome comprises a. GP1BA, in which case the secretome induces coagulation; b. TNFRSF21, SEMA7A, or a combination thereof, in which case the secretome induces cytokine production; c. f11R, in which case the secretome induces digestion; d. UNC5C, FSTL1, TNFRSF21, FST, MET, BSG, THBS1, FLT1, FSTL3, SEMA7A, or a combination thereof, in which case the secretome induces multicellular organism development; or e. TNFRSF21, FUR, KLK3, or a combination thereof, in which case the secretome induces a systemic process, are provided herein.

[0144]

[0146] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising excipients, wherein the secretome is a.XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, Compositions are provided herein that include CXCL1 or a combination thereof, in which case the secretome induces a cellular response to stimulation; or b. XCL1, CCL5, CCL20, CCL4, BCL10, CXCL5, TNFRSF21, PTX3, CCL13, IFNL1, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof, in which case the secretome induces an immune response.

[0145]

[0147] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising an excipient is provided herein, wherein the secretome comprises a. NID1, DKK1, DKK3, or a combination thereof, in which case the secretome induces intercellular signaling; or b. XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof, in which case the secretome induces signaling.

[0146]

[0148] a) Secretome at a concentration of approximately 0.1 w / w% or more, and b) Acceptable as a pharmaceutical product. A composition comprising excipients, wherein the secretome comprises a. furin, in which case the secretome is intended for use in treating Alzheimer's disease via the amyloid secretase pathway; b. FSTL1, furin, MMP1, or a combination thereof, in which case the secretome is intended for use in treating Alzheimer's disease via the presenilin pathway; c. PDGFB, ANGPT1, TF, or a combination thereof, in which case the secretome is intended for use in treating angiogenesis; d. BIRC2, FAS, TNFRSF1A, INFRSF10C, or a combination thereof, in which case the secretome is intended for use in inducing apoptosis or signaling; e. CXCL12, in which case the secretome induces Slit / Robo-mediated axonal guidance; f. UNC5C, in which case the secretome is mediated by netrin g. Induces mediated axonal guidance; including SERPINE1, PLAUR, GP1BA, THBD, KLK3, TF, or a combination thereof, in which case the secretome induces blood coagulation; h. Includes BIRC2, SERPINE1, CLU, CXCL1, or a combination thereof, in which case the secretome is intended for CCKR signaling; i. Includes FSTL1, in which case the secretome induces cadherin signaling; j. Includes furin, in which case the secretome induces the endothelin signaling pathway; k. FAS 1. Includes, in which case the secretome induces the FAS signaling pathway; 2. Includes TGFβ1, MIF, FST, INS, or a combination thereof, in which case the secretome induces the gonadotropin-releasing hormone receptor pathway; 3. Includes IL6, CCL5, CCL20, CCL4, CCL13, CCL8, CCL7, PF4, CCL26, or a combination thereof, in which case the secretome induces inflammation mediated by chemokine or cytokine signaling pathways; 4. Includes insulin (INS), in which case the secretome induces MAPK o. Contains insulin (INS), in which case the secretome induces the PKB signaling cascade; p. Contains IL6, IL21, or a combination thereof, in which case the secretome induces the interleukin signaling pathway; q. Contains PDGFB, in which case the secretome induces the PDGF signaling pathway; r. Contains SEREPIN1, PLAUR, MMP1, or a combination thereof, in which case the secretome induces the plasminogen activation cascade; s. Contains B2M, in which case, Compositions are provided herein in which a secretome induces T cell activation; t. TGFβ1, GDF15, or a combination thereof, in which case the secretome induces the TGF-beta signaling pathway; u. TLR3, in which case the secretome induces the Toll receptor signaling pathway; v. FSTL1, in which case the secretome induces the Wnt signaling pathway; or w. IGFBP3, SEREPINE1, FAS, THBS1, or a combination thereof, in which case the secretome induces the p53 pathway.

[0147]

[0149] Administering one of these compositions to a subject requiring administration of the composition. Methods comprising the above are provided herein. Uses of any of such compositions for treating subjects requiring treatment, or for manufacturing pharmaceuticals for treating subjects requiring treatment, are provided herein. Uses of any of such compositions for use in in vitro cultures or assays are provided herein.

[0148]

[0150] In any of these compositions, the composition may be substantially free of cells. Alternatively, the composition may be cell-free.

[0149]

[0151] The composition contains approximately 0.1% to 75% by weight, and approximately 0.1% to 65% by weight. It may be present in amounts of approximately 0.1% to 50% by weight, approximately 0.1% to 40% by weight, approximately 0.1% to 30% by weight, approximately 0.1% to 20% by weight, approximately 0.1% to 15% by weight, approximately 0.1% to 10% by weight, or approximately 0.1% to 5% by weight.

[0150]

[0152] In any of these embodiments, the secretome comprises at least one of the composition It may also constitute 0.6%, 1%, 1.25%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of the composition. In some cases, secretome constitutes about 0.6%, about 1%, about 1.25%, about 1.5%, about 2%, about 2.5%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% of the composition. In some cases, secretome constitutes approximately 0.6% to 25% of the composition, or approximately 2.5% to 10% of the composition.

[0151]

[0153] If the secretome contains more than one protein, each protein is: They may exist in ratios ranging from approximately 1:1 to approximately 20:1. For example, each protein may exist in ratios of approximately 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, or 20:1.

[0152]

[0154] In some cases, the compositions disclosed herein may be sterile. In some cases, the composition may contain one or more commensal microorganisms or cells. The one or more microorganisms or cells may be viruses, bacteria, eukaryotic cells, or any combination thereof. In some cases, the one or more microorganisms or cells may not be pathogenic. In some cases, the composition may contain one or more bacteria at concentrations of less than 10 colony-forming units (CFU) / gram (g), less than 50 CFU / g, less than 100 CFU / g, less than 150 CFU / g, less than 200 CFU / g, less than 300 CFU / g, less than 400 CFU / g, less than 500 CFU / g, less than 600 CFU / g, less than 700 CFU / g, less than 800 CFU / g, less than 900 CFU / g, or less than 1000 CFU / g. In some cases, the composition may contain bacteria at concentrations of approximately 10 CFU / g to approximately 1000 CFU / g, approximately 10 CFU / g to approximately 50 CFU / g, approximately 20 CFU / g to approximately 100 CFU / g, approximately 50 CFU / g to approximately 200 CFU / g, approximately 100 CFU / g to approximately 250 CFU / g, approximately 200 CFU / g to approximately 500 CFU / g, approximately 500 CFU / g to approximately 700 CFU / g, or approximately 600 CFU / g to approximately 1000 CFU / g. In some cases, the composition may be substantially free of or without Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, species of the genus Pseudomonas, Klebsiella pneumoniae, or any combination thereof.

[0153]

[0155] In some cases, the compositions disclosed herein are heavy metals, such as lead, and vinyl. The composition may not contain thionol, chlorofluorocarbon propellants, nitrosamines, chloroform, halogenated salicylanilide, hexachlorophene, mercury compounds, 1,4-dioxane, methylene chloride, prohibited bovine-derived materials, sunscreen compounds, vinyl chloride, zirconium-containing complexes, or any combination thereof. In some cases, prohibited bovine-derived materials may include brain, skull, eyes, trigeminal ganglion, spinal cord, vertebral column, dorsal root ganglion, tonsils, terminal ileum of the small intestine, or any combination thereof. In some cases, the composition may contain lead at a level of less than 10 ppm (parts per million).

[0154]

[0156] In some cases, the compositions described herein do not contain color additives. In some cases, the composition may contain color additives. In some cases, the composition may contain incidental components, such as color additives, in non-significant levels, for example, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or less than 0.1%. In some cases, incidental components do not have to have a technical / structural, functional, or any combination thereof effect in the composition; for example, incidental components are not active ingredients.

[0155]

[0157] In some cases, the composition contains protein at a concentration of 1 nanogram / milliliter Less than (ng / ml), less than 2 ng / ml, less than 3 ng / ml, less than 4 ng / ml, less than 5 ng / ml, less than 6 ng / ml, less than 7 ng / ml, less than 8 ng / ml, less than 9 ng / ml, less than 10 ng / ml, less than 11 ng / ml, less than 12 ng / ml, less than 13 ng / ml, less than 14 ng / ml, less than 15 ng / ml, less than 16 ng / ml, less than 17 ng / ml, less than 18 ng / ml, less than 19 ng / ml, less than 20 ng / ml, less than 21 ng / ml, less than 22 ng / ml, less than 23 ng / ml, less than 24 ng / ml, less than 25 ng / ml It may contain 1000 ng / ml at concentrations of 10,000 ng / ml, less than 30 ng / ml, less than 35 ng / ml, less than 40 ng / ml, less than 45 ng / ml, less than 50 ng / ml, less than 60 ng / ml, less than 70 ng / ml, less than 80 ng / ml, less than 90 ng / ml, less than 100 ng / ml, less than 200 ng / ml, less than 300 ng / ml, less than 400 ng / ml, less than 500 ng / ml, less than 600 ng / ml, less than 700 ng / ml, less than 800 ng / ml, less than 900 ng / ml, less than 1000 ng / ml, or 10000 ng / ml. In some cases, the direction may contain protein at concentrations of approximately 1 ng / ml to 100 ng / ml, approximately 10 ng / ml to 200 ng / ml, approximately 10 ng / ml to 400 ng / ml, approximately 50 ng / ml to 300 ng / ml, approximately 100 ng / ml to 200 ng / ml, approximately 150 ng / ml to 400 ng / ml, approximately 200 ng / ml to 600 ng / ml, approximately 400 ng / ml to 700 ng / ml, approximately 500 ng / ml to 900 ng / ml, approximately 600 ng / ml to 1000 ng / ml, approximately 900 ng / ml to 1500 ng / ml, or approximately 1000 ng / ml to 10000 ng / ml.

[0156]

[0158] In some cases, secretome is present in the composition at least 0.01%, 0 It may consist of 0.1%, 1%, 1.25%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99%. In some cases, secretome may constitute approximately 0.01% to 0.1%, approximately 0.01% to 1%, approximately 1% to 2%, approximately 1% to 5%, approximately 3% to 8%, approximately 5% to 10%, approximately 10% to 20%, approximately 20% to 40%, approximately 30% to 50%, approximately 50% to 75%, approximately 60% to 90%, approximately 75% to 95%, or approximately 80% to 99% of the composition.

[0157]

[0159] In some cases, the compositions described herein, exosomes, liposomes The exosomes may include liposomes, nanoparticles, or any combination thereof. In some cases, the liposomes may be in the form of nanoparticles. In some cases, the nanoparticles may contain liposomes. In some cases, the exosomes, liposomes, nanoparticles, or any combination thereof may contain secretomes, phospholipids, proteins, hydrophilic surfactants, hydrophilic surfactants, vitamins, inactive components, or any combination thereof. Examples of liposomes, but not limited to these, include monolayer liposomes, multilayer liposomes, archaeosomes, noosomes, novasomes, cryptosomes, emulsionsomes, besosomes, nanoliposomes, nanoemulsions, or any derivatives thereof, or any combination thereof. Examples of nanoparticles, but not limited to these, include biopolymer nanoparticles, alginate nanoparticles, xanthan gum nanoparticles, cellulose nanoparticles, lipid nanoparticles, dendrimers, polymer micelles, polyplexed inorganic nanoparticles, nanocrystals, metal nanoparticles, quantum dots, protein nanoparticles, polysaccharide nanoparticles, any derivatives thereof, or any combination thereof.

[0158]

[0160] In some cases, nanoparticles are less than 1 nanometer (nm) or less than 2 nm. , less than 3nm, less than 4nm, less than 5nm, less than 6nm, less than 7nm, less than 8nm, less than 9nm, less than 10nm, less than 11nm, less than 12nm, less than 13nm, less than 14nm, less than 15nm, less than 16nm, less than 17nm, less than 18nm, less than 19nm, less than 20nm, less than 21nm, less than 22nm, less than 23nm, less than 24nm, less than 25nm, less than 26nm, less than 27nm, less than 28nm, less than 29nm, less than 30nm, less than 35nm, less than 40nm, less than 45nm, less than 50nm, less than 60nm, less than 70nm, less than 80nm, less than 90nm, less than 100nm, less than 200nm, less than 300nm, less than 400nm, less than 500nm, less than 600nm, less than 700nm, less than 800nm, less than 900nm, or less than 1000nm. In some cases, nanoparticles are larger than 1 nanometer (nm), larger than 2 nm, larger than 3 nm, larger than 4 nm, and larger than 5 nm. Larger than 6nm, larger than 7nm, larger than 8nm, larger than 9nm, larger than 10nm, larger than 11nm, larger than 12nm, larger than 13nm, larger than 14nm, larger than 15nm, larger than 16nm, larger than 17nm, larger than 18nm, larger than 19nm, larger than 20nm, larger than 21nm, larger than 22nm, larger than 23nm, larger than 24nm, larger than 25nm, larger than 26nm, larger than 27nm, 28nm It may be greater than 1000nm, greater than 29nm, greater than 30nm, greater than 35nm, greater than 40nm, greater than 45nm, greater than 50nm, greater than 60nm, greater than 70nm, greater than 80nm, greater than 90nm, greater than 100nm, greater than 200nm, greater than 300nm, greater than 400nm, greater than 500nm, greater than 600nm, greater than 700nm, greater than 800nm, greater than 900nm, or greater than 1000nm. In some cases, the nanoparticles may have an average particle size of approximately 1 nm to 100 nm, approximately 10 nm to 200 nm, approximately 10 nm to 400 nm, approximately 50 nm to 300 nm, approximately 100 nm to 200 nm, approximately 150 nm to 400 nm, approximately 200 nm to 600 nm, approximately 400 nm to 700 nm, approximately 500 nm to 900 nm, approximately 600 nm to 1000 nm, or approximately 700 nm to 1500 nm. [Examples]

[0159]

[0161] This application refers to the following non-limiting examples provided as exemplary embodiments of this application. This can be better understood. The following embodiments are provided to illustrate the embodiments more completely, but should not be construed as limiting the scope of the present application.

[0160] Example 1 Secretome Composition Profile

[0162] MILLIPLEX MAP Human Cytokine / Chemok The secretome composition was determined from various stem cell culture extracts using a magnetic bead panel (Premixed 41 Plex-Immunology Multiplex assay). Concentrations were measured using Luminex LX200, and the results are shown in Figures 1A-1D and 2A-2C. The secretome analytes tested included sCD40L, EGF, eotaxin / CCL11, FGF-2, Flt-3 ligand, fractalkine, G-CSF, GM-CSF, GRO, IFN-α2, IFN-γ, IL-1α, IL-1β, IL-1Rα, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IL-17A, IP-10, MCP-1, MCP-3, MDC(CCL22), MIP-1α, MIP-1β, PDGF-AA, PDGF-AB / BB, RANTES, TGF-α, TNF-α, TNF-β, and VEGF. MCP-1 was found at high levels in the secretome. MCP-1 was present in a substantial portion of the secretome for use in formulations such as those described herein. Many other secretome proteins, such as GRO, IL-6, PDFG-AA, IL-8, MCP-3, and VEGF, were also identified at high concentrations. These secretome proteins may be used in formulations described herein.

[0161] Example 2 In vitro activity assay of secretome preparations

[0163] The MTT assay determines cell viability by evaluating the metabolic activity of cells. This is a colorimetric assay used for the purpose of ELISA. CCD-966SK human dermal fibroblasts derived from ATCC CRL-1881 were grown at 37°C for 48, 72, or 96 hours with a control, 0.625%, 1.25%, 2.5%, 5%, or 10% of exemplary secretome formulations disclosed herein. 150 μl of MTT (0.5 mg / ml) was then used in the ELISA. The results were obtained by reading at 595 nm using a DAR device, and are shown in Figure 3. Skin cell growth was significantly increased at secretome concentrations greater than 2.5% and after treatment for more than 72 hours. This increased growth suggests that secretome can enhance the growth of facial skin cells, thereby potentially reducing signs of aging such as wrinkles and age spots. Furthermore, the improved growth rate indicates that secretome may be used to increase the rate of wound healing.

[0162] Example 3 MCP-1 induced increased migration of skin cells in vitro.

[0164] Transwell migration assays were used to determine different inducers and inhibitors. The cellular migration response was tested. CCD-966SK human dermal fibroblasts derived from ATCC CRL-1881 were exposed to MCP-1 (100 ng / ml), and Transwell migration was determined at 4, 6, and 8 hours, compared to a control (without MCP-1). When MCP-1 was present in the Transwell assay, the migration of the tested dermal cells increased, as shown in Figure 4A. The results were statistically significant. ** p<0.01, *** (p<0.001). The cell image in Figure 4B for the culture in Figure 4A shows that MCP-1 induced increased migration of skin cells. Increased migration is useful for wound healing and swelling of the skin. MCP-1 may be added to the compositions described herein, at least in part, to reduce signs of aging, such as wrinkles and age spots.

[0163] Example 4 Cosmetic composition having nanoparticle delivery

[0165] The cosmetic composition is acceptable as a cosmetic, containing lipids and secretomes. The formulation includes nanoparticles carrying the active ingredient. Secretome proteins such as MCP-1, CXCL2, IL6, IL-8, and VEGF may be incorporated into the nanoparticles as passenger molecules, for example, using the method described herein. The nanoparticles may include amphiphilic, lipophilic, and hydrophilic passenger molecules. The nanoparticles may also be aggregates of phospholipids capable of encapsulating one or more active ingredients. The secretome-carrying nanoparticles may be combined with a carrier solution, such as glycerol and / or water. The cosmetic formulation may also contain vitamin B3 and vitamin A to potentially enhance its effects. Additional inactive ingredients may be added to form a cream. The cream may be packaged in a plastic vial. The subject may apply the cream to their face to prevent wrinkles and reduce their presence. Alternatively, inactive ingredients may be added to the formulation to form a liquid. The liquid may be applied to a patch. The patch may be packaged in a sealed container to prevent the formulated cosmetic patch from drying out. The patch can be applied to the face to prevent age-related wrinkles.

[0164] Example 5 Cosmetic composition having a liposome carrier

[0166] Cosmetic compositions include secretomes disclosed herein, such as protein MC. The formulation is prepared using a nanoliposome carrier encapsulating P-1, CXCL2, IL-6, IL-8, and VEGF. The nanoliposomes can be formed using the methods described herein. The nanoliposomes can be combined with a filler solution of saline and hyaluronic acid. Additional inactive ingredients may be added to form an injectable solution. The injectable solution can be packaged in a disposable dispenser or delivery tool such as a syringe. Medical professionals can treat subjects with intradermal injections containing the nanoliposome composition to reduce the presence of wrinkles.

[0165]

[0167] Another cosmetic composition is a single film encapsulating the secretome disclosed herein. It is formed by a posome carrier. A single-membrane liposome is a secretome protein, for example It may contain MCP-1, CXCL2, IL-6, IL-8, and VEGF. Single-layer liposomes can be formed using the methods described herein. Single-layer liposomes containing secretome proteins can be combined with linoleic acid and a carrier solution (e.g., polyethylene glycol). Further inactive ingredients may be added to form a butter. The butter can be packaged in an airtight container to prevent the cosmetic formulation from drying out. Cosmetic professionals may apply the butter to the target face to reduce the effects of skin aging.

[0166] Example 6 Regenerative medicine

[0168] The compositions described herein are used in regenerative medicines. Pharmaceutical formulations are used, for example, to treat liver failure. The pharmaceutical compositions are formulated using the secretomes disclosed herein. The pharmaceutical compositions may be formulated using secretome proteins, such as HEGF (heparin-bound epidermal growth factor), EGF (epidermal growth factor), HGF (hepatocyte growth factor), MCP-1, CXCL2 (GRO), VEGF, PDGF (e.g., PDGF-AA), IL-6, IL-8, or any combination thereof. The compositions contain pharmaceutically acceptable excipients, such as saline or phosphate buffer. The pharmaceutical compositions can be administered intravenously (IV) to treat hepatic failure. IV administration may be done daily. Secretome proteins can act as regenerative signals in the subject and promote liver healing. This treatment can, for example, alleviate hepatic scarring, hepatic fat deposition, cirrhosis, or any combination thereof, and reverse hepatic failure.

[0167]

[0169] Another pharmaceutical formulation is formulated using the secretome disclosed herein, and It is administered to subjects suffering from a stroke. This pharmaceutical composition can be formulated using secretome proteins, such as VEGF, EGF, NGF (neuronal growth factor), MCP-1, CXCL2 (GRO), PDGF (e.g., PDGF-AA), IL-6, IL-8, or any combination thereof. The composition contains pharmaceutically acceptable excipients, such as saline or phosphate buffers. The pharmaceutical composition can be administered intravenously after a stroke in a subject. The pharmaceutical composition may also be administered multiple times. Secretome proteins can act as regenerative signals in the subject and promote brain healing. This treatment can improve, for example, speech, coordination, cognition, or any combination thereof, and mitigate the effects of a stroke.

[0168]

[0170] Another pharmaceutical formulation is formulated using the secretome disclosed herein, The pharmaceutical composition is administered to the subject during surgery. The composition may be formulated using secretome proteins, such as VEGF, EGF, PDGF, MCP-1, CXCL2 (GRO), PDGF (e.g., PDGF-AA), IL-6, IL-8, or any combination thereof. The composition may contain pharmaceutically acceptable excipients, such as saline or phosphate buffers. The pharmaceutical composition may be applied to surgical wounds by spray. Secretome proteins may act as regenerative signals and promote wound healing. This treatment may promote wound healing, prevent infection at the surgical site, or a combination thereof.

[0169] Example 7 hTSC cell culture and secretome analysis

[0171] Human chorionic stem cell (hTSC) cell lineage (i.e., hTSC cell lineage 1, hTSC Cell lineage 2 and hTSC cell lineage 3) were grown in nutrient medium (e.g., MESENCULT®, with cell adhesion substrate) until confluence (e.g., approximately 3000 cells / cm²). 2 ~About 9000 cells / cm 2 , or approximately 6000 cells / cm 2). Wash the cells and replace the culture medium without supplementation. Induce hypoxia in the chamber (e.g., culture in a 2% O2 gas mixture for approximately 24 hours). Collect the culture medium and freeze until use. 3 Culture media from all cell lines were tested using a QUANTIBODY® Human Kiloplex Array (RAYBIOTECH® Life, Inc.), and 1000 proteins were quantitatively analyzed. The experiment was repeated for hTSC cell line 1 and hTSC cell line 2. Briefly, samples were processed, analyte concentrations (pg / mL) were determined, and compared to a standard curve. Data were determined as the percentage of samples below the limit of detection (LOD), the percentage of samples above the LOD but less than 3×LOD, the percentage of samples within the best confidence interval, and the percentage of samples exceeding the maximum value.

[0170]

[0172] Selected analytes with a concentration value of 80% or higher within the best confidence interval. Gene Onto Using logy analysis, 104 proteins were identified, grouped, and analyzed for protein class, biological process, and / or pathway. The results of the hypoxia test are shown in Table 1 below. Abbreviations: hTSC C1-exp.1 = hTSC cell lineage 1, experiment 1; hTSC C1-exp.2 = hTSC cell lineage 1, experiment 2; hTSC C2-exp.1 = hTSC cell lineage 2, experiment 1; hTSC C2-exp.2 = hTSC cell lineage 2, experiment 2; hTSC C3 = hTSC cell lineage 3.

[0171]

[0173]

[0172] [Table 1-1]

[0173] [Table 1-2]

[0174] [Table 1-3]

[0175] Table 1-4

[0176] Table 1-5

[0177] Table 1-6

[0178] Table 1-7

[0179] Table 1-8

[0180] Table 1-9

[0181] Table 1-10

[0182] Table 1-11

[0183] Table 1-12

[0184] Table 1-13

[0185] Table 1-14

[0186] Table 1-15

[0187] Table 1-16

[0188] Table 1-17

[0189] Table 1-18

[0190] Table 1-19

[0191] Table 1-20

[0192] Table 1-21

[0193] Table 1-22

[0194] Table 1-23

[0195] Table 1-24

[0196] Table 1-25

[0197] Table 1-26

[0198] Table 1-27

[0199] Table 1-28

[0200] Table 1-29

[0201] Table 1-30

[0202] Table 1-31

[0203] Table 1-32

[0204] Table 1-33

[0205] Table 1-34

[0206]

Table 1-35

[0207]

Table 1-36

[0208]

Table 1-37

[0209]

Table 1-38

[0210]

Table 1-39

[0211]

Table 1-40

[0212]

[0174] Exemplary determinations of gene functions and processes based on these results are shown in Table 2 below.

[0213]

[0175]

[0214]

Table 2-1

[0217] [Table 2-4]

[0218] [Table 2-5]

[0219] [Table 2-6]

[0220] [Table 2-7]

[0221] [Table 2-8]

[0222] [Table 2-9]

[0223] [Table 2-10]

[0224] [Table 2-11]

[0225] [Table 2-12]

[0226]

[0176] It has been found that hypoxia induces the expression of many proteins, and these proteins The substance can be used in secretomes as described above.

[0227]

[0177] Secretome is a promising cell-free alternative to cell-based therapies. Retome is dynamic in its therapeutic effects and can be designed and customized to suit its intended use in oncology, regenerative medicine, and medicated cosmetics.

[0228]

[0178] Although several embodiments are shown and described herein, such embodiments The embodiments are provided for illustrative purposes only. Numerous modifications, alterations, and substitutions are possible without departing from the present invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed when carrying out the invention.

Claims

1. 1) A composition comprising approximately 0.1 w / w% or more of secretome and 2) an excipient acceptable as a pharmaceutical or cosmetic, wherein the secretome comprises MCP-1 and the composition does not contain cells.

2. The composition according to claim 1, wherein the secretome further comprises one or more of the CXCL2 (GRO), IL-6, IL-8, and VEGF proteins.

3. The composition according to claim 1, wherein the secretome further comprises two of the following proteins: CXCL2 (GRO), IL-6, IL-8, and VEGF protein.

4. The composition according to claim 1, wherein the secretome further comprises three of the proteins CXCL2 (GRO), IL-6, IL-8, and VEGF.

5. The composition according to claim 1, wherein the secretome further comprises all of the following proteins: CXCL2 (GRO), IL-6, IL-8, and VEGF.

6. The composition according to any one of claims 1 to 5, wherein the secretome is present in the composition in an amount of at least 0.6% by weight, 1% by weight, 1.25% by weight, 1.5% by weight, 2% by weight, 2.5% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, or 20% by weight.

7. The composition according to any one of claims 1 to 6, wherein the secretome is present in the composition in an amount of about 2.5% to about 10% by weight.

8. The composition according to any one of claims 1 to 7, wherein the composition is a liquid or gel containing about 100 ng / ml to about 200 ng / ml of MCP-1.

9. (a) MCP-1, (b) one or more further proteins from among IL-6, VEGF, PDGF-AA, IL-8, or CXCL2 (GRO); and (c) pharmaceuticals Alternatively, a composition comprising an excipient acceptable as a cosmetic, wherein the ratio of MCP-1 to the one or more further proteins is in the range of about 30:1 to about 60:

1.

10. (a) MCP-1, CXCL2 (GRO), and one or more further proteins from among IL-8, MCP-3, IL-6, G-CSF, or VEGF; and (b) Excipients that are acceptable as pharmaceuticals or cosmetics A composition comprising the following: the ratio of MCP-1 to IL-8 is in the range of about 10:1 to about 7:1; the ratio of MCP-1 to MCP-3 is in the range of about 10:1 to about 30:1; the ratio of MCP-1 to IL-6 is in the range of about 30:1 to about 50:1; the ratio of MCP-1 to G-CSF is in the range of about 30:1 to about 50:1; the ratio of MCP-1 to VEGF is in the range of about 30:1 to about 50:1; CX A composition in which the ratio of CL2 to IL-8 is in the range of approximately 3:1 to approximately 4:1, the ratio of CXCL2 to MCP-3 is in the range of approximately 5:1 to approximately 15:1, the ratio of CXCL2 to IL-6 is in the range of approximately 10:1 to approximately 20:1, the ratio of CXCL2 to G-CSF is in the range of approximately 10:1 to approximately 20:1, the ratio of CXCL2 to VEGF is in the range of approximately 10:1 to approximately 20:1, or any combination thereof.

11. A composition comprising liposomes containing phospholipids and secretomes, and excipients acceptable as pharmaceuticals or cosmetics, wherein the composition is cell-free.

12. The composition according to claim 11, wherein the secretome is encapsulated in the liposome.

13. The composition according to claim 11 or 12, wherein the liposomes are in the form of nanoparticles.

14. The composition according to claim 13, wherein the nanoparticles have an average particle size of about 10 to about 400 nanometers in diameter.

15. The composition according to claim 14, wherein the nanoparticles have an average particle size of about 50 to about 300 nanometers in diameter.

16. The composition according to claim 15, wherein the nanoparticles have an average particle size of about 100 to about 200 nanometers in diameter.

17. The composition according to any one of claims 11 to 16, wherein the secretome comprises a chemokine, an interleukin, a growth factor, or any combination thereof.

18. The composition according to any one of claims 11 to 17, wherein the secretome comprises a microvesicle, an exosome, or a combination thereof.

19. The composition according to claim 18, wherein the secretome comprises the exosome, the exosome comprises a chemokine, and the chemokine comprises CXCL2 (GRO), MCP-1, fractalkine, IP-10, MCP-3, eotaxin, MIP-1β, or any combination thereof.

20. The composition according to claim 18 or 19, wherein the secretome comprises the exosome, and the exosome comprises an interleukin comprising IL-6, IL-8, IL-4, IL-1RA, IL-10, IL-12P40, IL-15, IL-1α, IL-17A, or any combination thereof.

21. The composition according to any one of claims 18 to 20, wherein the secretome comprises the exosome, and the exosome comprises a growth factor comprising PDGF-AA, VEGF, bFGF, G-CSF, Flt-3L, GM-CSF, or any combination thereof.

22. The composition according to any one of claims 11 to 21, wherein the secretome comprises MCP-1 and one, two, three, or all of the following proteins: CXCL2 (GRO), IL-6, IL-8, and VEGF.

23. The composition according to claim 22, wherein the secretome contains MCP-1 and CXCL2 in a weight ratio of about 1:1 to about 2:

1.

24. The composition according to claim 22, wherein the secretome contains MCP-1 and CXCL2 in a weight ratio of about 3:1 to about 4:

1.

25. The composition according to claim 22, wherein the secretome contains MCP-1 and IL-6 in a weight ratio of about 2:1 to about 3:

1.

26. The composition according to claim 22, wherein the secretome contains MCP-1 and IL-6 in a weight ratio of about 3:1 to about 4:

1.

27. The composition according to claim 22, wherein the secretome contains MCP-1 and IL-8 in a weight ratio of about 4:1 to about 6:

1.

28. The composition according to claim 22, wherein the secretome contains MCP-1 and VEGF in a weight ratio of about 4:1 to about 6:

1.

29. The composition according to claim 22, wherein the secretome contains MCP-1 and VEGF in a weight ratio of about 7:1 to about 9:

1.

30. The composition according to claim 22, wherein the secretome further comprises PDGF-AA, and MCP-1 and PDGF-AA are present in a weight ratio of about 3:1 to about 5:

1.

31. The composition according to claim 22, wherein the secretome further comprises PDGF-AA, and MCP-1 and PDGF-AA are present in a weight ratio of about 6:1 to about 9:

1.

32. The composition according to claim 22, wherein the secretome further comprises PDGF-AA, and MCP-1 and PDGF-AA are present in a weight ratio of about 30:1 to about 60:

1.

33. The composition according to claim 22, wherein the ratio of MCP-1 to any one of the CXCL2, IL-6, IL-8, and VEGF proteins is in the range of about 30:1 to about 60:

1.

34. The composition according to claim 22, wherein the secretome comprises MCP-1, CXCL2, IL-6, IL-8, and VEGF proteins.

35. The composition according to any one of claims 11 to 21, wherein the secretome comprises MCP-1, CXCL2 (GRO), and one, two, three, four, or all of the proteins IL-8, MCP-3, IL-6, G-CSF, and VEGF.

36. The composition according to claim 34, wherein the secretome contains MCP-1 and CXCL2 in a weight ratio of about 2:1 to about 3:

1.

37. The composition according to claim 34, wherein the secretome further comprises IL-8, the ratio of MCP-1 to IL-8 being in the range of about 10:1 to about 6:1 and / or the ratio of CXCL2 to IL-8 being in the range of about 3:1 to about 4:

1.

38. The composition according to claim 34, wherein the secretome further comprises MCP-3, the ratio of MCP-1 to MCP-3 being in the range of about 10:1 to about 30:1 and / or the ratio of CXCL2 to MCP-3 being in the range of about 5:1 to about 15:

1.

39. The composition according to claim 34, wherein the secretome further comprises IL-6, the ratio of MCP-1 to IL-6 is in the range of about 30:1 to about 50:1 and / or the ratio of CXCL2 to IL-6 is in the range of about 10:1 to about 20:

1.

40. The composition according to claim 35, wherein the secretome further comprises G-CSF, the ratio of MCP-1 to G-CSF being in the range of about 30:1 to about 50:1 and / or the ratio of CXCL2 to G-CSF being in the range of about 10:1 to about 20:

1.

41. The secretome further contains VEGF, and the ratio of MCP-1 to VEGF is approximately 30:

1. The composition according to claim 35, wherein the ratio is in the range of about 50:1, and the ratio of CXCL2 to VEGF is in the range of about 10:1 to about 20:

1.

42. The composition according to any one of the preceding claims, further comprising one or more proteins from among IP-10, eotaxin, Flt-3L, GM-CSF, MIP-1a, MIP-1b, IL-1a, IL-1RA, IL-4, IL-7, IL-10, IL-12P40, IL-13, IL-15, IL-17A, CCL5 (RANTES), MDC, MCP-3, IL-12P70, IFN-alpha, IFN-receptor, PDGF-AB / BB, or EGF.

43. A composition according to any one of claims 1 to 42, comprising a hydrophilic surfactant.

44. A composition according to any one of claims 1 to 43, comprising a vitamin.

45. A composition according to any one of claims 1 to 44, comprising a hydrophobic surfactant.

46. A composition according to any one of claims 1 to 45, comprising a fatty acid molecule.

47. A composition according to any one of claims 1 to 46, comprising linoleic acid.

48. A composition according to any one of claims 1 to 47, comprising collagen.

49. A composition according to any one of claims 1 to 48, comprising hyaluronic acid.

50. A composition according to any one of claims 1 to 49, which is free of serum, antibiotics, or a combination thereof.

51. A composition according to any one of claims 1 to 50, which does not contain steroids, cholesterol, choline hydrochloride, hypoxanthine sodium salt, thymidine, putrescine dihydrochloride, ferric nitrate, L-glutamine, or any combination thereof.

52. A composition according to any one of claims 1 to 51, which is free of color additives.

53. The composition according to any one of claims 1 to 52, wherein the dosage form is a lotion, cream, liquid, gel, emulsion, suspension, paste, stick, aerosol, foam, patch, powder, ointment, beads, mask, pad, sheet, wound dressing, bandage, or any combination thereof.

54. The composition according to any one of claims 1 to 53, wherein the excipients acceptable as pharmaceuticals or cosmetics include water, glycerol, seed oil, fruit oil, flower extract, mineral oil, synthetic oil, saccharide, silicate, calcium salt, magnesium salt, sodium chloride, sodium hydroxide, potassium chloride, lactose, lactic acid, starch, sugar alcohol, cellulose, activated carbon, amino acids, paraffin, honey, wax, beeswax, agar, calcium carbonate, citric acid, tartaric acid, stearic acid, xanthan gum, benzoic acid or its salts, polyethylene glycol, silicone, or any combination thereof.

55. A method for treating a disease or condition in a subject requiring such treatment, comprising the step of bringing a composition according to any one of claims 1 to 54 into contact with the subject requiring treatment.

56. The method according to claim 55, wherein a disease or condition is treated in the subject.

57. The method according to claim 55, which provides regenerative medicine.

58. The method according to claim 55 for treating stroke, myocardial infarction, hind limb ischemia, spinal cord injury, liver failure, or graft-versus-host disease (GVHD).

59. The method according to claim 55, for treating or improving the condition of the skin of the subject.

60. The method according to claim 59, wherein the condition is eczema, rash, psoriasis, acne, rosacea, ichthyosis, vitiligo, urticaria, seborrheic dermatitis, herpes zoster, burns, sunburn, contact dermatitis, wrinkled skin, scarred skin, loose skin, loss of skin elasticity, dry skin, dull skin, or any combination thereof.

61. The method according to any one of claims 55 to 60, wherein the subject is a human.

62. Use of the composition according to any one of claims 1 to 54 for the treatment of a subject requiring such treatment.

63. Use of the composition according to any one of claims 1 to 54 for the formulation of a medicine for the treatment of a subject requiring it.

64. The use according to claim 62 or 63 for treating a disease or condition in the subject.

65. Use according to any one of claims 62 to 64 for regenerative medicine.

66. The use according to any one of claims 62 to 64 for treating stroke, myocardial infarction, hind limb ischemia, spinal cord injury, liver failure, or graft-versus-host disease (GVHD).

67. The use according to any one of claims 62 to 64 for treating or improving the condition of the skin of the subject.

68. The use according to claim 67, wherein the condition is eczema, rash, psoriasis, acne, rosacea, ichthyosis, vitiligo, urticaria, seborrheic dermatitis, herpes zoster, burns, sunburn, contact dermatitis, wrinkled skin, scarred skin, loose skin, loss of skin elasticity, dry skin, dull skin, or any combination thereof.

69. The use according to any one of claims 62 to 68, wherein the subject is a human.

70. A method for producing one or more target proteins derived from trophoblast cell lines, a) A step of culturing human trophoblast stem cells in nutrient medium until the culture density is reached; b) A step to induce hypoxia; c) The step of isolating one or more target proteins from the culture medium. A method that includes this.

71. Low oxygen at 2% ２ The method according to claim 70, wherein the gas mixture is induced for approximately 24 hours.

72. The culture density is approximately 3,000 cells / cm³. ２ ~about 9,000 cells / cm ２ The method according to claim 70 or 71, including the method described in claim 70 or 71.

73. The method according to any one of claims 70 to 72, wherein the isolated protein or more is further mixed with one or more pharmaceutically acceptable excipients.

74. The method according to any one of claims 70 to 73, wherein the monoteria protein includes CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL15, Pf4, or any combination thereof.

75. The method according to any one of claims 70 to 73, wherein the one or more proteins include SPP1, DKK1, SERPINE1, FLT1, FSTL3, MATN3, PAPPA, GDF15, HGF, IGFBP3 or any combination thereof.

76. The method according to any one of claims 70 to 73, wherein the one or more proteins include FST, NID1, MET, TGFBI, FSTL1, NID2, CRIM1, PDGFB, or any combination thereof.

77. The method according to any one of claims 70 to 73, wherein the one or more proteins include CXCL12, LGALS1, ADAMTSL1, or any combination thereof.

78. The method according to any one of claims 70 to 73, wherein the one or more proteins include FAP, IGFBP3, or a combination thereof.

79. The method according to any one of claims 70 to 73, wherein the monoteria protein includes CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, PF4, or a combination thereof.

80. The method according to any one of claims 70 to 73, wherein the one or more proteins include CSF1, GDF15, IFNL1, IFNL2, IL21, IL6, MIF, NAMPT, SPP1, TGFB1, TIMP1, or a combination thereof.

81. The method according to any one of claims 70 to 73, wherein the one or more proteins include CSF1, CXCL12, DKK1, GDF15, HGF, IL6, PDGFB, TGFB1, TIMP1, or a combination thereof.

82. The method according to any one of claims 70 to 73, wherein the one or more proteins include ANG, CSTB, NAP1L4, TLR3, or a combination thereof.

83. The method according to any one of claims 70 to 73, wherein the one or more proteins include ADAMTSL1, DCN, FURIN, LUM, MATN3, MMP1, NID1, NID2, PDGFB, POSTN, PTX3, SERPINE, SPP1, TGFβI, THBS1, TIMP1, TIMP2, CCN1, LUM, MATN3, NID1, NID2, POSTN, or a combination thereof.

84. The aforementioned monoteri proteins are ANG, B2M, BCL10, CCL13, CCL20, CCL25, CCL28, CCL4, CD99, CLU, CSF1, CXCL1, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, F11R, F The method according to any one of claims 70 to 73, comprising AS, IFNL1, IFNL2, IL21, IL6, IL7R, LGALS3, MIF, OSCAR, PF4, PTX3, SERPINE1, SIGLEC9, THBS1, TLR3, TNFRSF21, or a combination thereof.

85. The method according to any one of claims 70 to 73, wherein the one or more proteins include CCL13, CCL13, CCL20, CCL25, CCL4, CCL5, CCL7, CCL8, CSF1, CXCL1, CXCL12, F11R, IGFBP4, IL6, MIF, NUP85, PF4, PTX3, SEMA7A, SPP1, THBS1, TNFRSF1A, or a combination thereof.

86. The method according to any one of claims 70 to 73, wherein the one or more proteins include ANG, CCL13, CCL20, CCL25, CCL26, CCL8, CLU, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, LGALS3, PF4, ANG, B2M, CCL20, KLK3, TLR3, TNFRSF1A, CCL4, IFNL1, IFNL2, IL21, IL6, TLR3, or a combination thereof.

87. The method according to any one of claims 70 to 73, wherein the one or more proteins include ANG, B2M, CCL20, KLK3, TLR3, TNFRSF1A, or any combination thereof.

88. The method according to any one of claims 70 to 73, wherein the one or more proteins include CCL4, IFNL1, IFNL2, IL21, IL6, TLR3, or any combination thereof.

89. The method according to any one of claims 70 to 73, wherein the one or more proteins include DCN, POSTN, SDC4, GRN, PAPPA, TIMP1, or a combination thereof.

90. The method according to any one of claims 70 to 73, wherein the one or more proteins include ANGPT1, FLT1, MET, CST3, DKK3, RBP4, BSG, or a combination thereof.

91. The method according to any one of claims 70 to 73, wherein the one or more proteins include ANG, DCN, BIRC2, PDGFB, or a combination thereof.

92. The method according to any one of claims 70 to 73, wherein the one or more proteins include TIMP4, CRIM1, UNC5C, TIMP2, or a combination thereof.

93. The method according to any one of claims 70 to 73, wherein the one or more proteins include DKK1, FST, TGFB1, FLT1, DKK3, CCN1, or a combination thereof.

94. The method according to any one of claims 70 to 73, wherein the one or more proteins include NAP1L4, SPP1, ANGPT1, FST, MET, CTSB, FSTL1, LGALS1, TPP1, OSCAR, CCN1, IGFBP3, TGFB1, B2M, IL7R, CES1, CSF1, or any combination thereof.

95. The method according to any one of claims 70 to 73, wherein the one or more proteins include SPP1, OSCAR, CCN1, IGFBP3, or any combination thereof.

96. The method according to any one of claims 70 to 73, wherein the one or more proteins include CSF1, MET, CCN1, TGFβ1, or LGALS1.

97. The method according to any one of claims 70 to 73, wherein the one or more proteins include B2M, IL7R, or a combination thereof.

98. The method according to any one of claims 70 to 73, wherein the one or more proteins include CTSB, TPP1, CES1, or a combination thereof.

99. The method according to any one of claims 70 to 73, wherein the one or more proteins include SIGLEC9, POSTN, TGFβI, or a combination thereof.

100. The method according to any one of claims 70 to 73, wherein the one or more proteins include OSCAR, B2M, or a combination thereof.

101. The method according to any one of claims 70 to 73, wherein the one or more proteins include LGALS3, LGALS1, or a combination thereof.

102. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, TGFβ1, CCL5, CCL20, CCL28, CCL4, CXCL5, ANGPTL4, PDGFB, CCL13, CCL8, ANGPTI, CCL25, CXCL11, CCL7, PF4, GDF15, CCL26, SEMA7A, SPP1, CXCL1, or a combination thereof.

103. The method according to any one of claims 70 to 73, wherein the monoterian protein includes XCL1, CCL5, CCL20, CCL28, CCL4, CXCL5, CCL13, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SPP1, CXCL1, or a combination thereof.

104. The method according to any one of claims 70 to 73, wherein the one or more proteins include TGFβI, PDGFB, GDF15, or a combination thereof.

105. The method according to any one of claims 70 to 73, wherein the one or more proteins comprise SEMA7A.

106. The method according to any one of claims 70 to 73, wherein the one or more proteins include CES1, FAS, MIF, NAMPT, SPP1, or a combination thereof.

107. The method according to any one of claims 70 to 73, wherein the one or more proteins include FAP, LGMN, HGF, CTSB, TPP1, KLK3, FURIN, MMP1, or a combination thereof.

108. The method according to any one of claims 70 to 73, wherein the one or more proteins include IGFBP3, TIMP4, FSTL1, BIRC2, FST, SERPINE1, TIMP1, IGFBP2, FSTL3, IGFBP4, TIMP2, or a combination thereof.

109. The method according to any one of claims 70 to 73, wherein the one or more proteins comprises BSG, NUP85, or LDLR.

110. The method according to any one of claims 70 to 73, wherein the one or more proteins include ALB, TPP1, LDLR, RBP4, TF, or a combination thereof.

111. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, TLR3, PLAUR, GP1BA, SDC4, THBD, IL7R, TF, or a combination thereof.

112. The method according to any one of claims 70 to 73, wherein the one or more proteins include SIGLEC9, CD99, TNFRSF21, GP1BA, BSG, POSTN, TGFβI, or a combination thereof.

113. The one or more of the aforementioned proteins are XCL1, IGFBP3, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, FST, SERPINE1, GP1BA, PDGFB, F11R, CCL13, TIMP1, NID1, CCL8, NUP85 The method according to any one of claims 70 to 73, comprising IGFBP6, THBS1, CCL25, IGFBP2, FSTL3, IGFBP4, KLK3, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, TIMP2, SEMA7A, FURIN, DKK1, INFRSF10C, CXCL1, or a combination thereof.

114. The method according to any one of claims 70 to 73, wherein the one or more proteins include TGFβ1, TNFRSF21, PDGFB, or a combination thereof.

115. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof.

116. The method according to any one of claims 70 to 73, wherein the one or more proteins include TNFRSF21, GP1BA, or a combination thereof.

117. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof.

118. The method according to any one of claims 70 to 73, wherein the one or more proteins include BIRC2, BCL10, LGALS3, TNFRSF21, INFRSF10C, or a combination thereof.

119. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof.

120. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof.

121. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, BSG, SEMA7A, or a combination thereof.

122. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, CCL26, TIMP2, SEMA7A, FURIN, or a combination thereof.

123. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof.

124. The method according to any one of claims 70 to 73, wherein the one or more proteins comprise TNFRSF21.

125. The method according to any one of claims 70 to 73, wherein the one or more proteins include TNFRSF21, GP1BA, or a combination thereof.

126. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof.

127. The method according to any one of claims 70 to 73, wherein the one or more proteins include BIRC2, BCL10, LGALS3, TNFRSF21, INFRSF10C, or a combination thereof.

128. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof.

129. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof.

130. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, BSG, SEMA7A, or a combination thereof.

131. The one or more proteins include XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, CCL26, TIMP2, SEMA7A, FURIN, or a combination thereof, according to any one of claims 70 to 73. method.

132. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof.

133. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof.

134. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, BSG, SEMA7A, or a combination thereof.

135. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof.

136. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, FSTL1, PTX3, TNFRSF21, FST, MET, FUR, BSG, THBS1, FLT1, FSTL3, SEMA7A, or a combination thereof.

137. The method according to any one of claims 70 to 73, wherein the one or more proteins comprise THBS1.

138. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, PTX3, BSG, THBS1, SEMA7A, or a combination thereof.

139. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof.

140. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, CCL5, CCL20, CCL4, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, PTX3, CCL13, IFNL1, CCL8, FLT1, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof.

141. The method according to any one of claims 70 to 73, wherein the one or more proteins include IFNL1, SEMA7A, or a combination thereof.

142. The aforementioned monoterian proteins are XCL1, CCL5, CCL20, CCL4, BCL10, CXCL5, TNFRSF21, PTX3, CCL13, IFNL1, CCL 8. The method according to any one of claims 70 to 73, comprising FLT1, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof.

143. The method according to any one of claims 70 to 73, wherein the one or more proteins comprise FLT1.

144. The method according to any one of claims 70 to 73, wherein the 1 or more proteins include XCL1, CCL5, CCL20, CCL4, BCL10, CD99, LGALS3, CXCL5, CCL13, CCL8, CXCL11, CCL7, PF4, CCL26, CXCL1, or a combination thereof.

145. The method according to any one of claims 70 to 73, wherein the one or more proteins include NUP85, GPC1, or a combination thereof.

146. The method according to any one of claims 70 to 73, wherein the one or more proteins include ALB, LGALS3, TNFRSF21, MET, F11R, NUP85, or a combination thereof.

147. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof.

148. The method according to any one of claims 70 to 73, wherein the one or more proteins include TNFRSF21, NUP85, GPC1, or a combination thereof.

149. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, or a combination thereof.

150. The method according to any one of claims 70 to 73, wherein the one or more proteins include CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof.

151. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, UNC5C, CCL5, CCL20, CCL4, LGALS3, CXCL5, CCL13, BSG, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof.

152. The method according to any one of claims 70 to 73, wherein the one or more proteins include TGFβ1, FSTL1, BCL10, FST, NUP85, FSTL3, GDF15, or a combination thereof.

153. The method according to any one of claims 70 to 73, wherein the one or more proteins include TIMP4, LGMN, CED1, TIMP1, CTSB, TIMP2, MMP1, or a combination thereof.

154. The aforementioned one or more proteins are XCL1, TGFβ1, CCL5, TIMP4, The method according to any one of claims 70 to 73, comprising CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, CCL26, TIMP2, SEMA7A, FURIN, or a combination thereof.

155. The method according to any one of claims 70 to 73, wherein the one or more proteins include FURIN.

156. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, or a combination thereof.

157. The method according to any one of claims 70 to 73, wherein the one or more proteins include CCL26, TIMP2, SEMA7A, FURIN, or a combination thereof.

158. The method according to any one of claims 70 to 73, wherein the monoterian protein includes XCL1, CCL5, CCL20, CCL4, CXCL5, PTX3, CCL13, IFNL1, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, CXCL1, or a combination thereof.

159. The method according to any one of claims 70 to 73, wherein the one or more proteins include GP1BA.

160. The method according to any one of claims 70 to 73, wherein the one or more proteins include TNFRSF21, SEMA7A, or a combination thereof.

161. The method according to any one of claims 70 to 73, wherein the one or more proteins include UNC5C, FSTL1, TNFRSF21, FST, MET, BSG, THBS1, FLT1, FSTL3, SEMA7A, or a combination thereof.

162. The method according to any one of claims 70 to 73, wherein the one or more proteins include TNFRSF21, FUR, KLK3, or a combination thereof.

163. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof.

164. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, CCL5, CCL20, CCL4, BCL10, CXCL5, TNFRSF21, PTX3, CCL13, IFNL1, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof.

165. The method according to any one of claims 70 to 73, wherein the one or more proteins include NID1, DKK1, DKK3, or a combination thereof.

166. The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or a combination thereof.

167. The method according to any one of claims 70 to 73, wherein the one or more proteins include FSTL1, FURIN, MMP1, or a combination thereof.

168. The method according to any one of claims 70 to 73, wherein the one or more proteins include PDGFB, ANGPT1, TF, or a combination thereof.

169. The method according to any one of claims 70 to 73, wherein the one or more proteins include BIRC2, FAS, TNFRSF1A, INFRSF10C, or a combination thereof.

170. The method according to any one of claims 70 to 73, wherein the one or more proteins comprise CXCL12.

171. The method according to any one of claims 70 to 73, wherein the one or more proteins comprises UNC5C.

172. The method according to any one of claims 70 to 73, wherein the one or more proteins include SERPINE1, PLAUR, GP1BA, THBD, KLK3, TF, or a combination thereof.

173. The method according to any one of claims 70 to 73, wherein the one or more proteins include BIRC2, SERPINE1, CLU, CXCL1, or a combination thereof.

174. The method according to any one of claims 70 to 73, wherein the one or more proteins comprise FSTL1.

175. The method according to any one of claims 70 to 73, wherein the one or more proteins comprise FAS.

176. The method according to any one of claims 70 to 73, wherein the one or more proteins include TGFβ1, macrophage migration inhibitory factor (MIF), follistatin (FST), insulin (INS), or a combination thereof.

177. The method according to any one of claims 70 to 73, wherein the monoterian protein comprises IL6, CCL5, CCL20, CCL4, CCL13, CCL8, CCL7, PF4, CCL26, or a combination thereof.

178. The method according to any one of claims 70 to 73, wherein the one or more proteins include insulin (INS).

179. The method according to any one of claims 70 to 73, wherein the one or more proteins include IL6, IL21, or a combination thereof.

180. The method according to any one of claims 70 to 73, wherein the one or more proteins include platelet-derived growth factor beta (PDGFβ).

181. The method according to any one of claims 70 to 73, wherein the one or more proteins include SEREPIN1, PLAUR, MMP1, or a combination thereof.

182. The method according to any one of claims 70 to 73, wherein the one or more proteins include β2-microglobulin (B2M).

183. The method according to any one of claims 70 to 73, wherein the one or more proteins include TGFβ1, GDF15, or a combination thereof.

184. The method according to any one of claims 70 to 73, wherein the one or more proteins include Toll-like receptor 3 (TLR3).

185. The method according to any one of claims 70 to 73, wherein the one or more proteins include follistatin-like 1 (FSTL1).

186. The method according to any one of claims 70 to 73, wherein the one or more proteins include IGFBP3, SEREPINE1, FAS, THBS1, or a combination thereof.

187. The method according to any one of claims 70 to 73, wherein the one or more proteins comprise F11R.

188. The method according to any one of claims 70 to 187, wherein the one or more proteins include cytokines, growth factors, membrane-bound signaling molecules, cell adhesion molecules, protective proteins, immune proteins, and extracellular matrix proteins, intracellular signaling molecules, metabolite interconversion enzymes, protein-modifying enzymes / proteases, protein-binding modulators / protease inhibitors, scaffold / adapter proteins, structural proteins, transport proteins or carrier proteins, transmembrane signal receptors, or any combination thereof.

189. a) a composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL15, PF4, or any combination thereof.

190. The composition according to claim 189, which is substantially free of cells or contains no cells.

191. The composition according to claim 189 or 190, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, thirteen, thirteen, thirteen, thirteen, thirteen, or fourteen of CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL15, and PF4.

192. The secretomes are CCL13, CCL20, CCL25, CCL26, and CCL28. The composition according to claim 189 or 190, comprising CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL15, and PF4.

193. The composition according to any one of claims 189 to 192, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

194. A method for inducing chemokine activity in a subject, comprising the step of administering a composition according to any one of claims 189 to 193 to a subject that requires induction of chemokine activity, wherein the composition induces chemokine activity in the subject.

195. Use of the composition according to any one of claims 189 to 193 for treating a subject requiring induction of chemokine activity, wherein the composition induces chemokine activity in the subject.

196. Use of the composition according to any one of claims 189 to 193 for the manufacture of a pharmaceutical for treating a subject requiring induction of chemokine activity, wherein the composition induces chemokine activity in the subject.

197. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of SPP1, DKK1, SERPINE1, FLT1, FSTL3, MATN3, PAPPA, GDF15, HGF, IGFBP3, or any combination thereof.

198. The composition according to claim 197, which is substantially free of cells or contains no cells.

199. The composition according to claim 197 or 198, wherein the secretome comprises one, two, three, four, five, six, seven, eight, or nine of SPP1, DKK1, SERPINE1, FLT1, FSTL3, MATN3, PAPPA, GDF15, HGF, and IGFBP3.

200. The composition according to claim 197 or 198, wherein the secretome comprises SPP1, DKK1, SERPINE1, FLT1, FSTL3, MATN3, PAPPA, GDF15, HGF, and IGFBP3.

201. The composition according to any one of claims 197 to 200, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

202. The composition according to any one of claims 197 to 201, wherein the secretome exhibits biased expression in the placenta.

203. A method comprising the step of administering a composition according to any one of claims 197 to 202 to a subject requiring administration of the composition, wherein the composition induces chemokine activity in the subject.

204. Use of the composition according to any one of claims 197 to 202 for treating an object that requires treatment.

205. Use of the composition according to any one of claims 197 to 202 for the manufacture of a pharmaceutical for treating an object requiring treatment.

206. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of FST, NID1, MET, TGFBI, FSTL1, NID2, CRIM1, PDGFB, or any combination thereof.

207. The composition according to claim 206, which is substantially free of cells or contains no cells.

208. The composition according to claim 206 or 207, wherein the secretome comprises one, two, three, four, five, six, or seven of FST, NID1, MET, TGFBI, FSTL1, NID2, CRIM1, and PDGFB.

209. The composition according to claim 206 or 207, wherein the secretome comprises FST, NID1, MET, TGFBI, FSTL1, NID2, CRIM1, and PDGFB.

210. The composition according to any one of claims 206 to 209, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

211. The composition according to any one of claims 206 to 210, wherein the secretome exhibits broad expression in the placenta.

212. A method comprising the step of administering a composition according to any one of claims 206 to 211 to a subject requiring administration of the composition.

213. Use of the composition according to any one of claims 206 to 211 for treating an object that requires treatment.

214. Use of the composition according to any one of claims 206 to 211 for the manufacture of a pharmaceutical for treating an object requiring treatment.

215. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of CXCL12, LGALS1, ADAMTSL1, or any combination thereof.

216. The composition according to claim 215, which is substantially free of cells or contains no cells.

217. The composition according to claim 215 or 216, wherein the secretome comprises one or two of CXCL12, LGALS1, and ADAMTSL1.

218. The composition according to claim 217, wherein the secretome comprises CXCL12, LGALS1, and ADAMTSL1.

219. The composition according to any one of claims 215 to 218, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

220. The composition according to any one of claims 215 to 219, wherein the secretome exhibits broad endometrial expression.

221. A method comprising the step of administering a composition according to any one of claims 217 to 220 to a subject requiring administration of the composition.

222. Use of the composition according to any one of claims 217 to 220 for treating an object that requires treatment.

223. Use of the composition according to any one of claims 217 to 220 for the manufacture of a pharmaceutical for treating an object requiring treatment.

224. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of FAP, IGFBP3, or a combination thereof.

225. The composition according to claim 224, which is substantially free of cells or contains no cells.

226. The composition according to claim 224 or 225, wherein the secretome comprises FAP or IGFBP3.

227. The composition according to claim 224 or 225, wherein the secretome comprises FAP and IGFBP3.

228. The composition according to any one of claims 224 to 227, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

229. The composition according to any one of claims 224 to 228, wherein the secretome exhibits biased endometrial expression.

230. A method comprising the step of administering a composition according to any one of claims 224 to 229 to a subject requiring administration of the composition.

231. Use of the composition according to any one of claims 224 to 229 for treating an object that requires treatment.

232. Use of the composition according to any one of claims 224 to 229 for the manufacture of a pharmaceutical for treating an object requiring treatment.

233. a) secretome at a concentration of approximately 0.1 w / w% or more and b) excipients that are acceptable as pharmaceuticals A composition comprising, wherein the secretome comprises one or more of CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, PF4, or a combination thereof.

234. The composition according to claim 233, which is substantially free of cells or contains no cells.

235. The composition according to claim 233 or 234, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, thirteen, fifteen, or fourteen of CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, and PF4.

236. The composition according to claim 235, wherein the secretome comprises CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, and PF4.

237. The composition according to any one of claims 233 to 236, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

238. A composition according to any one of claims 233 to 237, exhibiting chemokine activity.

239. A method comprising the step of administering a composition according to any one of claims 233 to 238 to a subject requiring administration of the composition.

240. Use of the composition according to any one of claims 233 to 238 for treating a subject requiring treatment who has a disease or condition that can be treated with chemokines.

241. Use of the composition according to any one of claims 233 to 238 for the manufacture of a pharmaceutical for treating an object requiring treatment, which has a disease or condition that can be treated with chemokines.

242. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of CSF1, GDF15, IFNL1, IFNL2, IL21, IL6, MIF, NAMPT, SPP1, TGFB1, TIMP1, or a combination thereof.

243. The composition according to claim 22, which is substantially free of cells or contains no cells.

244. The composition according to claim 242 or 243, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, or ten of CSF1, GDF15, IFNL1, IFNL2, IL21, IL6, MIF, NAMPT, SPP1, TGFB1, and TIMP1.

245. The composition according to claim 242 or 243, wherein the secretome comprises CSF1, GDF15, IFNL1, IFNL2, IL21, IL6, MIF, NAMPT, SPP1, TGFB1, and TIMP1.

246. The composition according to any one of claims 242 to 245, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

247. A composition according to any one of claims 242 to 246, which exhibits cytokine activity.

248. A method comprising the step of administering a composition according to any one of claims 242 to 246 to a subject requiring administration of the composition.

249. Use of the composition according to any one of claims 242 to 246 for treating a subject requiring treatment who has a disease or condition that can be treated with cytokines.

250. Use of the composition according to any one of claims 242 to 246 for the manufacture of a pharmacopoeia for treating a subject in need of treatment having a disease or condition that can be treated with cytokines.

251. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of CSF1, CXCL12, DKK1, GDF15, HGF, IL6, PDGFB, TGFB1, TIMP1, or a combination thereof.

252. The composition according to claim 251, which is substantially free of cells or contains no cells.

253. The composition according to claim 251 or 252, wherein the secretome comprises one, two, three, four, five, six, seven, or eight of CSF1, CXCL12, DKK1, GDF15, HGF, IL6, PDGFB, TGFB1, and TIMP1.

254. The composition according to claim 251 or 252, wherein the secretome comprises CSF1, CXCL12, DKK1, GDF15, HGF, IL6, PDGFB, TGFB1, and TIMP1.

255. The composition according to any one of claims 251 to 254, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

256. A composition according to any one of claims 251 to 255, comprising the growth factor secretome.

257. A method comprising the step of administering a composition according to any one of claims 251 to 256 to a subject requiring administration of the composition.

258. Use of the composition according to any one of claims 251 to 256 for treating a subject requiring treatment who has a disease or condition that can be treated with growth factors.

259. A composition according to any one of claims 251 to 256 for the manufacture of a pharmaceutical for treating a subject requiring treatment, having a disease or condition that can be treated with a growth factor. Use.

260. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of ANG, CSTB, NAP1L4, TLR3, or a combination thereof.

261. The composition according to claim 260, which is substantially free of cells or contains no cells.

262. The composition according to claim 260 or 261, wherein the secretome comprises one, two, or three of ANG, CSTB, NAP1L4, and TLR3.

263. The composition according to claim 262 or 261, wherein the secretome comprises ANG, CSTB, NAP1L4, and TLR3.

264. The composition according to any one of claims 260 to 263, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

265. A composition according to any one of claims 260 to 264, which induces RNA binding activity.

266. A method for inducing RNA binding activity in a subject requiring induction of RNA binding activity, comprising the step of administering a composition according to any one of claims 260 to 265 to the subject.

267. Use of the composition according to any one of claims 260 to 265 for inducing RNA binding activity in a target that requires induction of RNA binding activity.

268. Use of the composition according to any one of claims 260 to 265 for the manufacture of a pharmaceutical product for inducing RNA binding activity in a target requiring induction of RNA binding activity.

269. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) an excipient that is acceptable as a pharmaceutical, wherein the secretome comprises one or more of ADAMTSL1, DCN, FURIN, LUM, MATN3, MMP1, NID1, NID2, PDGFB, POSTN, PTX3, SERPINE, SPP1, TGFβI, THBS1, TIMP1, TIMP2, CCN1, LUM, MATN3, NID1, NID2, POSTN, or a combination thereof.

270. The composition according to claim 269, which is substantially free of cells or contains no cells.

271. The composition according to claim 269 or 270, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve

272. The secretomes are ADAMTSL1, DCN, FURIN, LUM, MATN3, MMP1, NID1, NID2, PDGFB, POSTN, PTX3, SERPINE, The composition according to claim 269 or 270, comprising SPP1, TGFβI, THBS1, TIMP1, TIMP2, CCN1, LUM, MATN3, and POSTN.

273. The composition according to any one of claims 269 to 272, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

274. A composition according to any one of claims 269 to 273, which induces extracellular matrix organization.

275. A method for inducing extracellular matrix organization in a subject requiring induction of extracellular matrix organization, comprising the step of administering a composition according to any one of claims 269 to 274 to a subject requiring administration of the composition.

276. Use of the composition according to any one of claims 269 to 274 for inducing extracellular matrix organization in subjects requiring induction of extracellular matrix organization.

277. Use of the composition according to any one of claims 269 to 274 for the manufacture of a pharmaceutical for inducing extracellular matrix organization in subjects requiring induction of extracellular matrix organization.

278. a) a secretome of about 0.1 w / w% or more and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of ANG, B2M, BCL10, CCL13, CCL20, CCL25, CCL28, CCL4, CD99, CLU, CSF1, CXCL1, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, F11R, FAS, IFNL1, IFNL2, IL21, IL6, IL7R, LGALS3, MIF, OSCAR, PF4, PTX3, SERPINE1, SIGLEC9, THBS1, TLR3, TNFRSF21, or a combination thereof.

279. The composition according to claim 278, which is substantially free of cells or contains no cells.

280. The secretomes are ANG, B2M, BCL10, CCL13, CCL20, CCL25, CCL28, CCL4, CD99, CLU, CSF1, CXCL1, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, F11R, FAS, IFNL1, IFNL2, IL21, IL6, IL7R, LGALS3, MIF, OSCAR, PF4, PTX3, The composition according to claim 278 or 279, comprising one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 of SERPINE1, SIGLEC9, THBS1, TLR3, and TNFRSF21.

281. The composition according to claim 280, wherein the secretome comprises ANG, B2M, BCL10, CCL13, CCL20, CCL25, CCL28, CCL4, CD99, CLU, CSF1, CXCL1, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, F11R, FAS, IFNL1, IFNL2, IL21, IL6, IL7R, LGALS3, MIF, OSCAR, PF4, PTX3, SERPINE1, SIGLEC9, THBS1, TLR3, and TNFRSF21.

282. The composition according to any one of claims 278 to 281, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

283. A composition according to any one of claims 268 to 282, which induces an immune response.

284. A method for inducing an immune response in a subject requiring induction of an immune response, comprising the step of administering a composition according to any one of claims 278 to 283 to a subject requiring administration of the composition.

285. Use of the composition according to any one of claims 278 to 283 for inducing an immune response in subjects requiring induction of an immune response.

286. Use of the composition according to any one of claims 278 to 283 for the manufacture of a pharmaceutical product for inducing an immune response in a subject requiring induction of an immune response.

287. a) a secretome of about 0.1 w / w% or more and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of the following, or a combination thereof: CCL13, CCL13, CCL20, CCL25, CCL4, CCL5, CCL7, CCL8, CSF1, CXCL1, CXCL12, F11R, IGFBP4, IL6, MIF, NUP85, PF4, PTX3, SEMA7A, SPP1, THBS1, TNFRSF1A.

288. The composition according to claim 287, which is substantially free of cells or contains no cells.

289. The composition according to claim 278 or 288, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve

290. The composition according to claim 287 or 288, wherein the secretome comprises CCL13, CCL13, CCL20, CCL25, CCL4, CCL5, CCL7, CCL8, CSF1, CXCL1, CXCL12, F11R, IGFBP4, IL6, MIF, NUP85, PF4, PTX3, SEMA7A, SPP1, THBS1, and TNFRSF1A.

291. The composition according to any one of claims 287 to 290, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

292. A composition according to any one of claims 287 to 291 for use in treating inflammation.

293. A method for treating inflammation in a subject requiring treatment for inflammation, according to claims 287- A method comprising the step of administering a composition according to any one of paragraphs 292 to a subject requiring administration of the composition.

294. Use of the composition according to any one of claims 287 to 292 for treating inflammation in a subject requiring treatment of inflammation.

295. Use of the composition according to any one of claims 287 to 292 for the manufacture of a pharmaceutical for treating inflammation in subjects requiring treatment of inflammation.

296. a) a secretome of about 0.1 w / w% or more and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of ANG, CCL13, CCL20, CCL25, CCL26, CCL8, CLU, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, LGALS3, PF4, ANG, B2M, CCL20, KLK3, TLR3, TNFRSF1A, CCL4, IFNL1, IFNL2, IL21, IL6, TLR3, or a combination thereof.

297. The composition according to claim 296, which is substantially free of cells or contains no cells.

298. The composition according to claim 296 or 297, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve

299. The composition according to claim 296 or 297, wherein the secretome comprises ANG, CCL13, CCL20, CCL25, CCL26, CCL8, CLU, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, LGALS3, PF4, ANG, B2M, CCL20, KLK3, TLR3, TNFRSF1A, CCL4, IFNL1, IFNL2, IL21, IL6, and TLR3.

300. A composition according to any one of claims 296 to 299, which is antibacterial.

301. The composition according to claim 296 or 297, wherein the secretome comprises one or more of ANG, B2M, CCL20, KLK3, TLR3, TNFRSF1A, or any combination thereof.

302. The composition according to claim 296 or 297, wherein the secretome comprises ANG, B2M, CCL20, KLK3, TLR3, and TNFRSF1A.

303. The composition according to claim 301 or 302, which is antibacterial.

304. The composition according to claim 296 or 297, wherein the secretome comprises one or more of CCL4, IFNL1, IFNL2, IL21, IL6, TLR3, or any combination thereof.

305. The composition according to claim 296 or 297, wherein the secretome comprises CCL4, IFNL1, IFNL2, IL21, IL6, and TLR3.

306. The composition according to claim 304 or 305, which is antiviral.

307. The composition according to any one of claims 296 to 306, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

308. A composition according to any one of claims 296 to 307 for use in treating microbial infections.

309. A method for treating a microbial infection in a subject requiring treatment for a microbial infection, comprising the step of administering a composition according to any one of claims 296 to 308 to the subject requiring administration of the composition.

310. Use of the composition according to any one of claims 296 to 308 for treating a microbial infection in a subject requiring treatment for a microbial infection.

311. Use of the composition according to any one of claims 296 to 308 for the manufacture of a pharmaceutical for treating microbial infections in subjects requiring treatment of microbial infections.

312. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of DCN, POSTN, SDC4, GRN, PAPPA, TIMP1, or a combination thereof.

313. The composition according to claim 312, which is substantially free of cells or contains no cells.

314. The composition according to claim 312 or 313, wherein the secretome comprises one, two, three, four, or five of DCN, POSTN, SDC4, GRN, PAPPA, and TIMP1.

315. The composition according to claim 312 or 313, wherein the secretome comprises DCN, POSTN, SDC4, GRN, PAPPA, and TIMP1.

316. The composition according to any one of claims 312 to 315, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

317. A composition according to any one of claims 312 to 315, which is useful for wound healing.

318. A method for wound healing in a subject requiring wound healing, comprising the step of administering a composition according to any one of claims 312 to 317 to a subject requiring administration of the composition.

319. Use of the composition according to any one of claims 312 to 317 for wound healing in subjects requiring wound healing.

320. Claim 31 for the manufacture of a pharmaceutical product for wound healing in subjects requiring wound healing Use of the composition described in any one of items 2 to 317.

321. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of ANGPT1, FLT1, MET, CST3, DKK3, RBP4, BSG, or a combination thereof.

322. The composition according to claim 321, which is substantially free of cells or contains no cells.

323. The composition according to claim 321 or 322, wherein the secretome comprises one, two, three, four, five, or six of ANGPT1, FLT1, MET, CST3, DKK3, RBP4, and BSG.

324. The composition according to claim 321 or 322, wherein the secretome comprises ANGPT1, FLT1, MET, CST3, DKK3, RBP4, and BSG.

325. The composition according to any one of claims 321 to 324, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

326. A composition according to any one of claims 321 to 325, which is useful for inducing embryonic development.

327. A method for inducing embryonic development in a subject requiring induction of embryonic development, comprising the step of administering a composition according to any one of claims 321 to 326 to a subject requiring administration of the composition.

328. Use of the composition according to any one of claims 321 to 326 for inducing embryonic development in subjects requiring induction of embryonic development.

329. Use of the composition according to any one of claims 321 to 326 for the manufacture of a pharmaceutical for inducing embryogenesis in subjects requiring induction of embryogenesis.

330. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of ANG, DCN, BIRC2, PDGFB, or a combination thereof.

331. The composition according to claim 330, which is substantially free of cells or contains no cells.

332. The composition according to claim 330 or 331, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelf or twelf.

333. The composition according to claim 330 or 331, wherein the secretome comprises ANG, DCN, BIRC2, and PDGFB.

334. The secretome is present in amounts of approximately 0.1% to 75% by weight, approximately 0.1% to 65% by weight, approximately 0.1% to 50% by weight, approximately 0.1% to 40% by weight, approximately 0.1% to 30% by weight, approximately 0.1% to 20% by weight, approximately 0.1% to 15% by weight, and approximately 0.1% by weight. The composition according to any one of claims 330 to 333, wherein the composition contains in an amount of weight % to about 10% by weight, or about 0.1% to about 5% by weight.

335. A composition according to any one of claims 330 to 334, which is useful for inducing placental development.

336. A method for inducing placental development in a subject requiring induction of placental development, comprising the step of administering a composition according to any one of claims 330 to 335 to a subject requiring administration of the composition.

337. Use of the composition according to any one of claims 330 to 335 for inducing placental development in subjects requiring induction of placental development.

338. Use of the composition according to any one of claims 330 to 335 for the manufacture of a pharmaceutical product for inducing placental development in subjects requiring induction of placental development.

339. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of TIMP4, CRIM1, UNC5C, TIMP2, or a combination thereof.

340. The composition according to claim 339, which is substantially free of cells or contains no cells.

341. The composition according to claim 339 or 340, wherein the secretome comprises one, two, or three of TIMP4, CRIM1, UNC5C, and TIMP2.

342. The composition according to claim 339 or 340, wherein the secretome comprises TIMP4, CRIM1, UNC5C, and TIMP2.

343. The composition according to any one of claims 339 to 342, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

344. A composition according to any one of claims 339 to 343, which is useful for inducing central nervous system (CNS) development.

345. A method for inducing CNS development in a subject requiring CNS development, comprising the step of administering a composition according to any one of claims 339 to 344 to a subject requiring administration of the composition.

346. Use of the composition according to any one of claims 339 to 344 for inducing CNS development in subjects requiring CNS development induction.

347. Use of the composition according to any one of claims 339 to 344 for the manufacture of a pharmaceutical for inducing CNS development in subjects requiring induction of CNS development.

348. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) an excipient that is acceptable as a pharmaceutical, wherein the secretome comprises one or more of DKK1, FST, TGFB1, FLT1, DKK3, CCN1, or a combination thereof.

349. The composition according to claim 348, which is substantially free of cells or contains no cells.

350. The composition according to claim 348 or 349, wherein the secretome comprises one, two, three, four, or five of DKK1, FST, TGFB1, FLT1, DKK3, and CCN1.

351. The composition according to claim 348 or 349, wherein the secretome comprises DKK1, FST, TGFB1, FLT1, DKK3, and CCN1.

352. The composition according to any one of claims 348 to 351, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

353. A composition according to any one of claims 348 to 352, which is useful for inducing morphogenesis.

354. A method for inducing morphogenesis in a subject requiring morphogenesis induction, comprising the step of administering a composition according to any one of claims 348 to 353 to a subject requiring administration of the composition.

355. Use of the composition according to any one of claims 348 to 353 for inducing morphogenesis in an object that requires induction of morphogenesis.

356. Use of the composition according to any one of claims 348 to 353 for the manufacture of a pharmaceutical for inducing morphogenesis in subjects requiring induction of morphogenesis.

357. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) an excipient that is acceptable as a pharmaceutical, wherein the secretome comprises one or more of NAP1L4, SPP1, ANGPT1, FST, MET, CTSB, FSTL1, LGALS1, TPP1, OSCAR, CCN1, IGFBP3, TGFB1, B2M, IL7R, CES1, CSF1, or any combination thereof.

358. The composition according to claim 357, which is substantially free of cells or contains no cells.

359. The composition according to claim 357 or 358, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, t

360. The composition according to claim 357 or 358, wherein the secretome comprises NAP1L4, SPP1, ANGPT1, FST, MET, CTSB, FSTL1, LGALS1, TPP1, OSCAR, CCN1, IGFBP3, TGFB1, B2M, IL7R, CES1, and CSF1.

361. The composition according to any one of claims 357 to 360, wherein the secretome induces the differentiation of stem cells.

362. The composition according to any one of claims 357 or 358, wherein the secretome comprises one or more of SPP1, OSCAR, CCN1, IGFBP3, or any combination thereof.

363. The composition according to claim 362, wherein the secretome comprises SPP1, OSCAR, CCN1, and IGFBP3.

364. The composition according to claim 362 or 363, which induces the differentiation of stem cells into osteoblasts.

365. The composition according to claim 357 or 358, wherein the secretome comprises CSF1.

366. The composition according to claim 364, which induces the differentiation of stem cells into osteoclasts or macrophages.

367. The composition according to claim 357 or 358, wherein the secretome comprises B2M, IL7R, or a combination thereof.

368. The composition according to claim 357 or 358, wherein the secretome comprises B2M and IL7R.

369. The composition according to claim 367 or 368, which induces the differentiation of stem cells into T cells.

370. The composition according to claim 357 or 358, wherein the secretome comprises one or more of CTSB, TPP1, CES1, or any combination thereof.

371. The composition according to claim 370, wherein the secretome comprises CTSB, TPP1, and CES1.

372. The composition according to claim 370 or 371, which induces differentiation of stem cells into epithelial cells.

373. The composition according to claim 357 or 358, wherein the secretome comprises MET.

374. The composition according to claim 373, which induces the differentiation of stem cells into nerve cells.

375. The composition according to claim 357 or 358, wherein the secretome comprises CCN1.

376. The composition according to claim 375, which induces the differentiation of stem cells into chondrocytes.

377. The composition according to claim 357 or 358, wherein the secretome comprises TGFβ1.

378. The composition according to claim 377, which induces the differentiation of stem cells into chondrocytes.

379. The composition according to claim 357 or 358, wherein the secretome comprises LGALS1.

380. The composition according to claim 379, which induces the differentiation of stem cells into myoblasts.

381. The secretome is present in amounts of approximately 0.1% to 75% by weight, approximately 0.1% to 65% by weight, approximately 0.1% to 50% by weight, approximately 0.1% to 40% by weight, approximately 0.1% to 30% by weight, approximately 0.1% to 20% by weight, approximately 0.1% to 15% by weight, and approximately 0.1% by weight. The composition according to any one of claims 357 to 380, wherein the composition contains in an amount of weight % to about 10% by weight, or about 0.1% to about 5% by weight.

382. A method for inducing cell differentiation in a subject requiring induction of cell differentiation, in vitro, ex vivo, or in vivo, comprising the step of administering a composition according to any one of claims 357 to 381.

383. Use of the composition according to any one of claims 357 to 381 for inducing cell differentiation in vitro, ex vivo, or in vivo in subjects requiring induction of cell differentiation.

384. Use of the composition according to any one of claims 357 to 381 for the manufacture of a pharmaceutical product for inducing cell differentiation in vitro, ex vivo, or in vivo in subjects requiring induction of cell differentiation.

385. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of SIGLEC9, POSTN, TGFβI, or a combination thereof.

386. The composition according to claim 385, which is substantially free of cells or contains no cells.

387. The composition according to claim 385 or 386, wherein the secretome comprises one or two of SIGLEC9, POSTN, and TGFβI.

388. The composition according to claim 385 or 386, wherein the secretome comprises SIGLEC9, POSTN, and TGFβI.

389. The composition according to any one of claims 385 to 388, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

390. A method for inducing or promoting cell adhesion in a subject requiring induction or promotion of cell adhesion, comprising the step of administering a composition according to any one of claims 385 to 389 to a subject requiring administration of the composition.

391. Use of the composition according to any one of claims 385 to 389 for inducing or promoting cell adhesion in a subject requiring induction or promotion of cell adhesion, or for the manufacture of a pharmaceutical for inducing or promoting cell adhesion in a subject requiring induction or promotion of cell adhesion.

392. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) an excipient that is acceptable as a pharmaceutical, wherein the secretome comprises one or more of OSCAR, B2M, or a combination thereof.

393. The composition according to claim 392, which is substantially free of cells or contains no cells.

394. The composition according to claim 392 or 393, wherein the secretome comprises OSCAR or B2M.

395. The composition according to claim 392 or 393, wherein the secretome comprises OSCAR and B2M.

396. The composition according to any one of claims 392 to 395, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

397. A method for improving or enhancing immunity in a subject requiring improvement or enhancement of immunity, comprising the step of administering a composition according to any one of claims 392 to 396 to a subject requiring administration of the composition.

398. Use of the composition according to any one of claims 392 to 396 for improving or enhancing an object that requires improvement or enhancement, or for the manufacture of a pharmaceutical for improving or enhancing an object that requires improvement or enhancement.

399. a) A composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of LGALS3, LGALS1, or a combination thereof.

400. The composition according to claim 399, which is substantially free of cells or contains no cells.

401. The composition according to claim 399 or 400, wherein the secretome comprises LGALS3 or LGALS1.

402. The composition according to claim 399 or 400, wherein the secretome comprises LGALS3 and LGALS1.

403. The composition according to any one of claims 399 to 402, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

404. A method for inducing or enhancing the extracellular matrix in a subject requiring induction or enhancement of the extracellular matrix, comprising the step of administering a composition according to any one of claims 399 to 403 to a subject requiring administration of the composition.

405. Use of the composition according to any one of claims 399 to 403 for inducing or enhancing the extracellular matrix in subjects requiring induction or enhancement of the extracellular matrix, or for the manufacture of a pharmacopoeia for inducing or enhancing the extracellular matrix in subjects requiring induction or enhancement of the extracellular matrix.

406. a) a secretome of about 0.1 w / w% or more and b) an excipient that is acceptable as a pharmaceutical, wherein the secretome includes one or more of XCL1, TGFβ1, CCL5, CCL20, CCL28, CCL4, CXCL5, ANGPTL4, PDGFB, CCL13, CCL8, ANGPTI, CCL25, CXCL11, CCL7, PF4, GDF15, CCL26, SEMA7A, SPP1, CXCL1, or a combination thereof. A finished product.

407. The composition according to claim 406, which is substantially free of cells or contains no cells.

408. The composition according to claim 406 or 407, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve

409. The composition according to claim 406 or 407, wherein the secretome comprises XCL1, TGFβ1, CCL5, CCL20, CCL28, CCL4, CXCL5, ANGPTL4, PDGFB, CCL13, CCL8, ANGPTI, CCL25, CXCL11, CCL7, PF4, GDF15, CCL26, SEMA7A, SPP1, and CXCL1.

410. The composition according to claim 406 or 407, wherein the secretome contains cytokine activity, and the secretome comprises XCL1, CCL5, CCL20, CCL28, CCL4, CXCL5, CCL13, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SPP1, CXCL1, or a combination thereof.

411. The composition according to claim 406 or 407, wherein the secretome contains cytokine activity, and the secretome comprises XCL1, CCL5, CCL20, CCL28, CCL4, CXCL5, CCL13, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SPP1, and CXCL1.

412. The composition according to claim 406 or 407, wherein the secretome contains growth factor activity, and the secretome comprises TGFβI, PDGFB, GDF15, or a combination thereof.

413. The composition according to claim 406 or 407, wherein the secretome contains growth factor activity, and the secretome comprises TGFβI, PDGFB, and GDF15.

414. The composition according to claim 406 or 407, wherein the secretome comprises a signal transduction molecule, and the secretome comprises SEMA7A.

415. The composition according to any one of claims 406 to 414, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

416. A method for inducing or enhancing intracellular signaling in a subject requiring induction or enhancement of intracellular signaling, comprising the step of administering a composition according to any one of claims 406 to 415 to a subject requiring administration of the composition.

417. Use of the composition according to any one of claims 406 to 415 for inducing or enhancing intracellular signaling in subjects requiring induction or enhancement of intracellular signaling, or for the manufacture of a pharmacopoeia for inducing or enhancing intracellular signaling in subjects requiring induction or enhancement of intracellular signaling.

418. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of CES1, FAS, MIF, NAMPT, SPP1, or a combination thereof.

419. The composition according to claim 418, which is substantially free of cells or contains no cells.

420. The composition according to claim 418 or 419, wherein the secretome comprises one, two, three, or four of CES1, FAS, MIF, NAMPT, and SPP1.

421. The composition according to claim 418 or 419, wherein the secretome comprises CES1, FAS, MIF, NAMPT, and SPP1.

422. The composition according to any one of claims 418 to 421, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

423. A method for inducing or enhancing the activity of metabolite reciprocating enzymes in a subject requiring induction or enhancement of the activity of metabolite reciprocating enzymes, comprising the step of administering a composition according to any one of claims 418 to 422 to a subject requiring administration of the composition.

424. Use of the composition according to any one of claims 418 to 422 for inducing or enhancing the activity of metabolite reciprocating enzymes in subjects requiring induction or enhancement of the activity of metabolite reciprocating enzymes, or for the manufacture of a pharmaceutical product for inducing or enhancing the activity of metabolite reciprocating enzymes in subjects requiring induction or enhancement of the activity of metabolite reciprocating enzymes.

425. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of FAP, LGMN, HGF, CTSB, TPP1, KLK3, FURIN, MMP1, or a combination thereof.

426. The composition according to claim 425, which is substantially free of cells or contains no cells.

427. The composition according to claim 425 or 426, wherein the secretome comprises one, two, three, four, five, six, or seven of FAP, LGMN, HGF, CTSB, TPP1, KLK3, FURIN, and MMP1.

428. The composition according to claim 425 or 426, wherein the secretome comprises FAP, LGMN, HGF, CTSB, TPP1, KLK3, FURIN, and MMP1.

429. The composition according to any one of claims 425 to 428, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

430. A method for inducing or enhancing the activity of a protein-modifying enzyme / protease in a subject requiring induction or enhancement of the activity of a protein-modifying enzyme / protease, comprising administering the composition according to any one of claims 425 to 429 to the subject requiring administration of the composition. A method that includes the steps to do so.

431. Use of the composition according to any one of claims 425 to 429 for inducing or enhancing the activity of a protein-modifying enzyme / protease in a subject requiring induction or enhancement of the activity of a protein-modifying enzyme / protease, or for the manufacture of a pharmaceutical for inducing or enhancing the activity of a protein-modifying enzyme / protease in a subject requiring induction or enhancement of the activity of a protein-modifying enzyme / protease.

432. a) a composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of IGFBP3, TIMP4, FSTL1, BIRC2, FST, SERPINE1, TIMP1, IGFBP2, FSTL3, IGFBP4, TIMP2, or a combination thereof.

433. The composition according to claim 432, which is substantially free of cells or contains no cells.

434. The composition according to claim 432 or 433, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, or ten of IGFBP3, TIMP4, FSTL1, BIRC2, FST, SERPINE1, TIMP1, IGFBP2, FSTL3, IGFBP4, and TIMP2.

435. The composition according to claim 432 or 433, wherein the secretome comprises IGFBP3, TIMP4, FSTL1, BIRC2, FST, SERPINE1, TIMP1, IGFBP2, FSTL3, IGFBP4, and TIMP2.

436. The composition according to any one of claims 432 to 435, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

437. A method for inducing or enhancing the activity of a protein-binding modulator / protease inhibitor in a subject requiring induction or enhancement of the activity of the protein-binding modulator / protease inhibitor, comprising the step of administering a composition according to any one of claims 432 to 436 to a subject requiring administration of the composition.

438. Use of the composition according to any one of claims 432 to 437 for the manufacture of a pharmacopoeia for inducing or enhancing the activity of a protein-binding modulator / protease inhibitor in a subject requiring induction or enhancement of the activity of a protein-binding modulator / protease inhibitor, or for the manufacture of a pharmacopoeia for inducing or enhancing the activity of a protein-binding modulator / protease inhibitor in a subject requiring induction or enhancement of the activity of a protein-binding modulator / protease inhibitor.

439. a) A composition comprising approximately 0.1 w / w% or more of secretome and b) an excipient that is acceptable as a pharmaceutical, wherein the secretome contains BSG.

440. The composition according to claim 439, which is substantially free of cells or contains no cells.

441. The secretome is present in amounts of approximately 0.1% to 75% by weight, approximately 0.1% to 65% by weight, approximately 0.1% to 50% by weight, approximately 0.1% to 40% by weight, approximately 0.1% to 30% by weight, approximately 0.1% to 20% by weight, approximately 0.1% to 15% by weight, and approximately 0.1% by weight. The composition according to claim 439 or 440, wherein the component is present in the composition in an amount of weight % to about 10% by weight, or about 0.1% to about 5% by weight.

442. A method for inducing or enhancing the activity of a scaffold / adapter protein in a subject requiring induction or enhancement of the activity of the scaffold / adapter protein, comprising the step of administering a composition according to any one of claims 439 to 441 to a subject requiring administration of the composition.

443. Use of the composition according to any one of claims 439 to 441 for inducing or enhancing the activity of a scaffold / adapter protein in a subject requiring induction or enhancement of the activity of the scaffold / adapter protein, or for the manufacture of a pharmaceutical for inducing or enhancing the activity of a scaffold / adapter protein in a subject requiring induction or enhancement of the activity of the scaffold / adapter protein.

444. a) A composition comprising approximately 0.1 w / w% or more of secretome and b) an excipient that is acceptable as a pharmaceutical, wherein the secretome comprises NUP85.

445. The composition according to claim 444, which is substantially free of cells or contains no cells.

446. The composition according to claim 444 or 445, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

447. A method for inducing or enhancing the activity of a structural protein in a subject requiring induction or enhancement of the activity of a structural protein, comprising the step of administering a composition according to any one of claims 444 to 446 to a subject requiring administration of the composition.

448. Use of the composition according to any one of claims 444 to 446 for inducing or enhancing the activity of structural proteins in subjects where induction or enhancement of structural protein activity is required, or for the manufacture of a pharmaceutical for inducing or enhancing the activity of structural proteins in subjects where induction or enhancement of structural protein activity is required.

449. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) an excipient that is acceptable as a pharmaceutical, wherein the secretome comprises one or more of ALB, TPP1, LDLR, RBP4, TF, or a combination thereof.

450. The composition according to claim 449, which is substantially free of cells or contains no cells.

451. The composition according to claim 449 or 450, wherein the secretome comprises one, two, three, or four of ALB, TPP1, LDLR, RBP4, and TF.

452. The composition according to any one of claims 449 to 451, wherein the secretome comprises LDLR.

453. The composition according to claim 449 or 450, wherein the secretome comprises ALB, TPP1, LDLR, RBP4, and TF.

454. The composition according to any one of claims 449 to 453, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

455. A method for inducing or enhancing the activity of a transport / carrier protein in a subject requiring induction or enhancement of the activity of the transport / carrier protein, comprising the step of administering a composition according to any one of claims 449 to 454 to a subject requiring administration of the composition.

456. Use of the composition according to any one of claims 449 to 453 for inducing or enhancing the activity of transport / carrier proteins in subjects requiring induction or enhancement of transport / carrier protein activity, or for the manufacture of a pharmacopoeia for inducing or enhancing the activity of transport / carrier proteins in subjects requiring induction or enhancement of transport / carrier protein activity.

457. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of UNC5C, TLR3, PLAUR, GP1BA, SDC4, THBD, IL7R, TF, or a combination thereof.

458. The composition according to claim 457, which is substantially free of cells or contains no cells.

459. The composition according to claim 457 or 458, wherein the secretome comprises one, two, three, four, five, six, or seven of UNC5C, TLR3, PLAUR, GP1BA, SDC4, THBD, IL7R, and TF.

460. The composition according to claim 457 or 458, wherein the secretome comprises UNC5C, TLR3, PLAUR, GP1BA, SDC4, THBD, IL7R, and TF.

461. The composition according to any one of claims 457 to 460, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

462. A method for inducing or enhancing the activity of a transmembrane signal receptor in a subject requiring induction or enhancement of the activity of a transmembrane signal receptor, comprising the step of administering a composition according to any one of claims 457 to 461 to a subject requiring administration of the composition.

463. Use of the composition according to any one of claims 457 to 461 for inducing or enhancing the activity of transmembrane signal receptors in subjects requiring induction or enhancement of transmembrane signal receptor activity, or for the manufacture of a pharmacopoeia for inducing or enhancing the activity of transmembrane signal receptors in subjects requiring induction or enhancement of transmembrane signal receptor activity.

464. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of SIGLEC9, CD99, TNFRSF21, GP1BA, BSG, POSTN, TGFβI, or a combination thereof.

465. The composition according to claim 464, which is substantially free of cells or contains no cells.

466. The composition according to claim 464 or 465, wherein the secretome comprises one, two, three, four, five, or six of the following: SIGLEC9, CD99, TNFRSF21, GP1BA, BSG, POSTN, and TGFβI.

467. The composition according to claim 464 or 465, wherein the secretome comprises SIGLEC9, CD99, TNFRSF21, GP1BA, BSG, POSTN, and TGFβI.

468. The composition according to any one of claims 464 to 467, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

469. A method for inducing cell adhesion in a subject requiring induction of cell adhesion, comprising the step of administering a composition according to any one of claims 464 to 468 to a subject requiring administration of the composition.

470. Use of the composition according to any one of claims 464 to 468 for inducing cell adhesion in a subject requiring induction of cell adhesion, or for the manufacture of a pharmaceutical for inducing cell adhesion in a subject requiring induction of cell adhesion.

471. a) a secretome of about 0.1 w / w% or more and b) an excipient that is acceptable as a pharmaceutical, wherein the secretome is XCL1, IGFBP3, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, FST, SERPINE1, GP1BA, PDGFB, F11R, CCL13, A composition comprising one or more of the following, or a combination thereof: TIMP1, NID1, CCL8, NUP85, IGFBP6, THBS1, CCL25, IGFBP2, FSTL3, IGFBP4, KLK3, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, TIMP2, SEMA7A, FURIN, DKK1, INFRSF10C, CXCL1.

472. The composition according to claim 471, which is substantially free of cells or contains no cells.

473. The secretome is XCL1, IGFBP3, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, FST, SERPINE1, GP1BA, PDGFB, F11R, CCL13, TIMP1, NID1, CCL8, NUP85, IGFBP6, THBS1, CCL25, IGFBP2, FSTL3, IGFBP4, KLK3, CXCL11, GPC1, CCL7, DKK3, PF 4. The composition according to claim 471 or 472, comprising one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or 44 from among GDF15, TF, CCL26, TIMP2, SEMA7A, FURIN, DKK1, INFRSF10C, and CXCL1.

474. The secretomes are XCL1, IGFBP3, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, FST, SERPINE1, GP1BA, PDGFB, F11R, CCL13, TIMP1, NID1, CCL8, NUP85 The composition according to claim 471 or 472, comprising IGFBP6, THBS1, CCL25, IGFBP2, FSTL3, IGFBP4, KLK3, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, TIMP2, SEMA7A, FURIN, DKK1, INFRSF10C, and CXCL1.

475. The composition according to any one of claims 471 to 474, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

476. A method for inducing biological regulation in a subject requiring the induction of biological regulation, comprising the step of administering a composition according to any one of claims 471 to 475 to a subject requiring the administration of the composition.

477. Use of the composition according to any one of claims 471 to 475 for inducing bioregulation in subjects requiring induction of bioregulation, or for the manufacture of a pharmaceutical product for inducing bioregulation in subjects requiring induction of bioregulation.

478. a) A composition comprising approximately 0.1 w / w% or more of a secretome and b) an excipient that is acceptable as a pharmaceutical, wherein the secretome comprises one or more of TGFβ1, TNFRSF21, PDGFB, or a combination thereof.

479. The composition according to claim 478, which is substantially free of cells or contains no cells.

480. The composition according to claim 478 or 479, wherein the secretome comprises one or two of TGFβ1, TNFRSF21, and PDGFB.

481. The composition according to claim 478 or 479, wherein the secretome comprises TGFβ1, TNFRSF21, and PDGFB.

482. The composition according to any one of claims 478 to 481, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

483. A method for inducing cell proliferation in a subject requiring induction of cell proliferation, comprising the step of administering a composition according to any one of claims 478 to 482 to a subject requiring administration of the composition.

484. Use of the composition according to any one of claims 478 to 482 for inducing cell proliferation in subjects requiring induction of cell proliferation, or for the manufacture of a pharmaceutical product for inducing cell proliferation in subjects requiring induction of cell proliferation.

485. a) secretome at a concentration of approximately 0.1 w / w% or more and b) excipients that are acceptable as pharmaceuticals A composition comprising, wherein the secretome comprises one or more of UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof.

486. The composition according to claim 485, which is substantially free of cells or contains no cells.

487. The composition according to claim 485 or 486, wherein the secretome comprises one, two, three, four, five, six, or seven of UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, and MMP1.

488. The composition according to claim 485 or 486, wherein the secretome comprises UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, and MMP1.

489. The composition according to any one of claims 485 to 488, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

490. A method for inducing cell organization or biodevelopment in a subject requiring induction of cell organization or biodevelopment, comprising the step of administering a composition according to any one of claims 485 to 489 to a subject requiring administration of the composition.

491. Use of the composition according to any one of claims 485 to 489 for inducing cell organization or biodevelopment in subjects requiring induction of cell organization or biodevelopment, or for the manufacture of a pharmaceutical product for inducing cell organization or biodevelopment in subjects requiring induction of cell organization or biodevelopment.

492. a) comprising approximately 0.1 w / w% or more of secretome and b) excipients that are acceptable as pharmaceuticals, wherein the secretome is a. TNFRSF21, GP1BA, or a combination thereof; the secretome induces cell activation; b. XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or any combination thereof, the secretome induces cellular communication; c. BIRC2, the secretome, induces cell cycle processes or microtubule-based processes; d. BIRC2, BCL10, LGALS3, TNFRSF21, INFRSF10C, or any combination thereof, the secretome induces cell death; e. SEMA7A, the secretome induces cell growth; f. UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof, the secretome induces cellular component organization; g. UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof, the secretome induces cell development processes; h. UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof, the secretome induces cell differentiation; i. UNC5C, BSG, SEMA7A, or a combination thereof, the secretome induces morphogenesis; j. XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, CCL26, TIMP2, SEMA7A, FURIN, or any combination thereof, the secretome induces cellular metabolic processes; k. XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or any combination thereof, the secretome induces a cellular response to stimulation; l. TNFRSF21, the secretome induces export from the cell; m. TNFRSF21, GP1BA, or a combination thereof, the secretome induces cell activation; or n. XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or any combination thereof, the secretome induces cellular communication; A composition containing the following:

493. a) comprising approximately 0.1 w / w% or more of secretome and b) excipients that are acceptable as pharmaceuticals, wherein the secretome is a. XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or any combination thereof, the secretome induces cell motility; b. UNC5C, BSG, SEMA7A, or a combination thereof, the secretome induces neuronal projection guidance; c. TNFRSF21, the secretome induces myelin formation; or d. XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or any combination thereof, the secretome induces signal transduction; A composition containing the following:

494. a) comprising approximately 0.1 w / w% or more of secretome and b) excipients that are acceptable as pharmaceuticals, wherein the secretome is a. UNC5C, FSTL1, PTX3, TNFRSF21, FST, MET, FUR, BSG, THBS1, FLT1, FSTL3, SEMA7A, or any combination thereof, the secretome induces the developmental process; b. UNC5C, FSTL1, PTX3, TNFRSF21, FST, MET, FUR, BSG, THBS1, FLT1, FSTL3, SEMA7A, or any combination thereof. The secretome induces the expression of anatomical structures; c. THBS1, the secretome, induces the formation of anatomical structures involved in morphogenesis; d. UNC5C, PTX3, BSG, THBS1, SEMA7A, or a combination thereof, the secretome induces anatomical morphogenesis; e. UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or any combination thereof, the secretome induces a cell development process; or f. SEMA7A, or a combination thereof, the secretome induces growth; A composition containing the following:

495. a) comprising approximately 0.1 w / w% or more of secretome and b) excipients that are acceptable as pharmaceuticals, wherein the secretome is a. IFNL1, SEMA7A, or a combination thereof, the secretome induces an immunoeffector process; b. XCL1, CCL5, CCL20, CCL4, BCL10, CXCL5, TNFRSF21, PTX3, CCL13, IFNL1, CCL8, FLT1, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or any combination thereof, the secretome induces an immune response; c. FLT1, the secretome, induces the development of the immune system; d. TNFRSF21, the secretome induces leukocyte activation; or e. XCL1, CCL5, CCL20, CCL4, BCL10, CD99, LGALS3, CXCL5, CCL13, CCL8, CXCL11, CCL7, PF4, CCL26, CXCL1, or any combination thereof, the secretome induces leukocyte migration; A composition containing the following:

496. a) comprising approximately 0.1 w / w% or more of secretome and b) excipients that are acceptable as pharmaceuticals, wherein the secretome is a. NUP85, GPC1, or a combination thereof, the secretome induces cellular localization; b. ALB, LGALS3, TNFRSF21, MET, F11R, NUP85, or a combination thereof, the secretome induces the establishment of localization; c. XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or any combination thereof, the secretome induces cell localization; d. TNFRSF21, NUP85, GPC1, or a combination thereof, the secretome induces macromolecule localization; e. XCL1, CCL5, CCL20, CCL4, CD99, LGALS3, CXCL5, MET, PDGFB, CCL13, SDC4, CCL8, or any combination thereof, the secretome induces cell motility; f. CCL25, CXCL11, GPC1, CCL7, PF4, CCL26, SEMA7A, CXCL1, or any combination thereof; or g. XCL1, UNC5C, CCL5, CCL20, CCL4, LGALS3, CXCL5, CCL13, BSG, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or any combination thereof, the secretome induces chemotaxis; A composition containing the following:

497. a) secretome at a concentration of approximately 0.1 w / w% or more and b) excipients that are acceptable as pharmaceuticals Including the secretome, a. TGFβ1, FSTL1, BCL10, FST, NUP85, FSTL3, GDF15, or a combination thereof; the secretome induces the biosynthetic process; b. TIMP4, LGMN, CED1, TIMP1, CTSB, TIMP2, MMP1, or a combination thereof, the secretome induces catabolic processes; c. XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, CCL26, TIMP2, SEMA7A, FURIN, or any combination thereof, the secretome induces cellular metabolic processes; d. Furin, the secretome induces hormonal metabolic processes; e. XCL1, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, LGMN, FST, SERPINE1, PDGFB, CCL13, TIMP1, CCL8, CTSB, NUP85, CCL25, FSTL3, CCL7, GDF15, or any combination thereof, the secretome induces nitrogen compound metabolic processes; or f. CCL26, TIMP2, SEMA7A, FURIN, or any combination thereof; A composition containing the following:

498. a) a composition comprising about 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises XCL1, CCL5, CCL20, CCL4, CXCL5, PTX3, CCL13, IFNL1, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, CXCL1, or a combination thereof.

499. a) comprising approximately 0.1 w / w% or more of secretome and b) excipients that are acceptable as pharmaceuticals, wherein the secretome is a. GP1BA, the secretome, induces coagulation; b. TNFRSF21, SEMA7A, or a combination thereof; the secretome induces cytokine production; c. f11R, the secretome induces digestion; d. UNC5C, FSTL1, TNFRSF21, FST, MET, BSG, THBS1, FLT1, FSTL3, SEMA7A, or any combination thereof, the secretome induces multicellular organism development; or e. TNFRSF21, FUR, KLK3, or a combination thereof, the secretome induces a system process; A composition containing the following:

500. a) comprising approximately 0.1 w / w% or more of secretome and b) excipients that are acceptable as pharmaceuticals, wherein the secretome is a. XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or any combination thereof, the secretome induces a cellular response to stimulation; or b. XCL1, CCL5, CCL20, CCL4, BCL10, CXCL5, TNFRSF21, PTX3, CCL13, IFNL1, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or any combination thereof, the secretome induces an immune response; A composition containing the following:

501. a) comprising approximately 0.1 w / w% or more of secretome and b) excipients that are acceptable as pharmaceuticals, wherein the secretome is a. NID1, DKK1, DKK3, or a combination thereof, the secretome induces intercellular signaling; or b. XCL1, IGFBP3, TGFβ1, CCL5, CCL20, FSTL1, CCL4, BCL10, LGALS3, CXCL5, FST, PDGFB, CCL13, NID1, CCL8, IGFBP6, CCL25, IGFBP2, FSTL3, IGFBP4, CXCL11, GPC1, CCL7, DKK3, PF4, GDF15, TF, CCL26, SEMA7A, DKK1, INFRSF10C, CXCL1, or any combination thereof, the secretome induces signal transduction; A composition containing the following:

502. a) comprising approximately 0.1 w / w% or more of secretome and b) excipients that are acceptable as pharmaceuticals, wherein the secretome is c. FURIN, the secretome, is intended for use in treating Alzheimer's disease via the amyloid secretion pathway; d. FSTL1, FURIN, MMP1, or a combination thereof, the secretome is intended for use in treating Alzheimer's disease via the presenilin pathway; e. PDGFB, ANGPT1, TF, or a combination thereof; the secretome is intended for use in treating angiogenesis; f. BIRC2, FAS, TNFRSF1A, INFRSF10C, or a combination thereof, the secretome is intended for use in inducing or signaling apoptosis; g. CXCL12, the secretome induces axonal guidance mediated by Slit / Robo; h. UNC5C, the secretome induces netrin-mediated axonal guidance; i. SERPINE1, PLAUR, GP1BA, THBD, KLK3, TF, or a combination thereof, the secretome induces blood coagulation; j. BIRC2, SERPINE1, CLU, CXCL1, or a combination thereof, the secretome is intended for CCKR signaling; k. FSTL1, the secretome, induces cadherin signaling; l. FURIN, the secretome, induces the endothelin signaling pathway; m. FAS, the secretome induces the FAS signaling pathway; n. TGFβ1, MIF, FST, INS, or a combination thereof; the secretome induces the gonadotropin-releasing hormone receptor pathway; o. IL6, CCL5, CCL20, CCL4, CCL13, CCL8, CCL7, PF4, CCL26, or any combination thereof, the secretome induces inflammation mediated by chemokine or cytokine signaling pathways; p. Insulin (INS), the secretome, induces the MAPKK / MAPK cascade; q. Insulin (INS), the secretome, induces the PKB signaling cascade; r. IL6, IL21, or a combination thereof, the secretome induces the interleukin signaling pathway; s. PDGFB, the secretome, induces the PDGF signaling pathway; t. SEREPIN1, PLAUR, MMP1, or a combination thereof, the secretome induces a plasminogen activation cascade; u. B2M, the secretome induces T cell activation; v. TGFβ1, GDF15, or a combination thereof, the secretome induces the TGF-beta signaling pathway; w. TLR3, the secretome, induces the Toll receptor signaling pathway; x. FSTL1, the secretome induces the Wnt signaling pathway; or y. IGFBP3, SEREPINE1, FAS, THBS1, or a combination thereof, the secretome induces the p53 pathway; A composition containing the following:

503. A composition according to any one of claims 492 to 502, which is substantially free of cells or contains no cells.

504. The composition according to any one of claims 492 to 503, wherein the secretome is present in the composition in an amount of about 0.1% to about 75% by weight, about 0.1% to about 65% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, about 0.1% to about 15% by weight, about 0.1% to about 10% by weight, or about 0.1% to about 5% by weight.

505. A method comprising the step of administering a composition according to any one of claims 492 to 504 to a subject requiring administration of the composition.

506. Use of the composition according to any one of claims 492 to 504 for treating an object requiring treatment, or for the manufacture of a pharmacopoeia for treating an object requiring treatment.

507. Use of the composition according to any one of claims 492 to 504 for use in in vitro culture or assay.

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