Pharmaceutical and cosmetic compositions containing secretome

Abstract

Pharmaceutical or cosmetic compositions containing secretomes, e.g., proteins secreted from stem cells, and their uses are disclosed. The compositions containing secretomes and acceptable excipients may be cell-free. The compositions are useful for inducing immune responses, treating inflammatory responses, treating microbial infections, differentiating cells, wound healing, embryonic development, placental development, central nervous system development, or morphogenesis.

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 project] 【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, compositions are disclosed herein that comprise MCP-1 and one or more further proteins selected from IL-6, VEGF, platelet-derived growth factor AA (PDGF-AA), IL-8, or CXCL2 (GRO), as well as excipients that are acceptable as pharmaceuticals or cosmetics, wherein the ratio of MCP-1 to the 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 to 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 to 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 to 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 to 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 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. 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 the ratio of MCP-1 to IL-8 ranging from approximately 10:1 to approximately 6:1 and / or the ratio of CXCL2 to IL-8 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 ranging from approximately 30:1 to approximately 50:1 and / or a CXCL2 to G-CSF ratio ranging from 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 an CXCL2 to VEGF ratio in the range of approximately 10:1 to approximately 20:1. In some cases, the composition further contains 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 signal 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 methods described is useful in one or more of the following pathways: Alzheimer's disease-amyloid secretion enzyme pathway; Alzheimer's disease-presenilin pathway; angiogenesis; apoptosis signaling pathway; 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. 【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 from about 0.6% to about 25% of the composition, or from 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 may contain bacteria at concentrations of approximately 10 CFU / g to 1000 CFU / g, approximately 10 CFU / g to 50 CFU / g, approximately 20 CFU / g to 100 CFU / g, approximately 50 CFU / g to 200 CFU / g, approximately 100 CFU / g to 250 CFU / g, approximately 200 CFU / g to 500 CFU / g, approximately 500 CFU / g to 700 CFU / g, or approximately 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 salicylanilides, 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, 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 less than 10 parts per million (ppm). 【0023】 In some cases, the compositions herein 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 be taken up in 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 cases, the secretome can constitute approximately 0.01% to 0.1%, 0.01% to 1%, 1% to 2%, 1% to 5%, 3% to 8%, 5% to 10%, 10% to 20%, 20% to 40%, 30% to 50%, 50% to 75%, 60% to 90%, 75% to 95%, or 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 will be obtained by referring to the following detailed description, which describes exemplary embodiments in which the principles of the present invention are utilized, and the 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 described in the accompanying drawings, claims, and description herein. The features, compounds, compositions, methods, and advantages of the disclosure of the 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 and scientific terms used herein have the same meaning as that generally understood by those skilled in the art of the claimed subject matter. The above general descriptions and the following detailed descriptions, which are expected to be understood as such, are illustrative and descriptive only and do not limit any of the claimed subject matter. 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, compositions comprising a secretome, e.g., proteins, exosomes, microvesicles, secreted from a cell or population of cells (e.g., stem cells of the examples) 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. In some cases, the secretome is purified or extracted from a stem cell culture or 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 have an average particle size of less than about 500 nm, for example, less than about 250 nm, or for example, about 50 to about 150 nm. In some cases, the composition comprises 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, compositions are disclosed herein that comprise 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 the weight ratio of MCP-1 to each of the 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 these, can facilitate one or more stages of wound healing, such as inflammation (e.g., ROS-mediated), granular ECM formation, wound closure, and / or remodeling of ECM remodeling enhancement.

[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 about 2:1 to about 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 about 10:1 to about 6:1, and / or the weight ratio of CXCL2 to IL-8 in the secretome or composition is in the range of about 3:1 to about 4:1. In some cases, the secretome further comprises MCP-3 and / or CXCL2, and the weight ratio of MCP-1 to MCP-3 in the secretome or composition is 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 is 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 ranging from about 30:1 to about 50:1, and / or the weight ratio of CXCL2 to IL-6 in the secretome or composition ranging from 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, the weight ratio of MCP-1 to VEGF in the secretome or composition is in the range of about 30:1 to about 50:1, and the weight ratio of CXCL2 to VEGF in the secretome or composition is in the range of 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 compositions contain linoleic acid. In some cases, the compositions contain collagen. In some cases, the compositions contain 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 substantially lack, or be free of, Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, species of the genus Pseudomonas, Klebsiella pneumoniae, or any combination thereof.

[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 contain alpha hydroxy acids, beta hydroxy acids, diethanolamine (DEA), talc, or any combination thereof. In some cases, the beta hydroxy acid may be salicylic acid, beta hydroxybutanoic acid, tropic acid, tretocanic acid, their salts, or any combination thereof. In some cases, the diethanolamine may contain cocamide DEA, cocamide monoethanolamine (MEA), cetyl phosphate DEA, oleth-3 phosphate DEA, lauramide DEA, linoleamide MEA, myristamide DEA, oleamide DEA, stearamide MEA, lauryl sulfate TEA, triethanolamine, their salts, or any combination thereof. In some cases, the compositions may contain 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 may be free of fragrances, parabens, phthalates, alcohol, 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 derived from stem cells. 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 may be grown in vitro, for example, in cell culture. In some cases, the secretome may contain proteins or fragments of which there are no 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, emulsionosomes, 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.

[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), 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, diflorazone, fluocinolone, hydrocortisone, halcinonide, mometasone, triamcinolone, its derivatives, 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, 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 composition further includes glyceryl monostearate 40-50, hydroxypropylcellulose, hypromellose, magnesium stearate, methacrylate copolymer type C, polysorbate 80, sugar spheres, talc, or triethyl citrate. In some cases, the composition further comprises 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 oxides, 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, whether biodegradable, partially biodegradable, or non-biodegradable, 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. In some cases, the pH of the liquid compositions disclosed herein 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 multi-dose dosage forms. 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 multi-dose dosage form 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 of multi-dose dosage forms, but not limited to, include vials, bottles of tablets or capsules, or bottles of several pints or several gallons. In some cases, a multi-dose dosage form contains different pharmaceutically acceptable 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 in a ratio of approximately 6.5:2.5:0.7:0.3. In some cases, 1 gram of 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 per 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 preparing amphiphilic carrier structures represented as Solvent Dilution Microcarriers (SDMCs). In some cases, the SDMC may have a diameter of approximately 230 to 412 nm.In some cases, nanoliposomes may have an average diameter of about 1 nm to about 20 nm, and nanoliposome aggregates may have an average diameter of about 30 nm to about 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, a method is disclosed herein that includes the step of administering a composition disclosed herein to a subject (e.g., a human) that requires administration of the composition. In some cases, the method treats a disease in the subject. In some cases, the method restores the condition of the subject's 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, repair, or any combination thereof of the glycosaminoglycans, dermis, collagen, and elastin of the skin. In some cases, the improved health of the skin can be measured by a wrinkle severity scale, transepidermal water loss measurement, skin color measurement, skin surface morphometry, viscoelasticity measurement by CUTOMETER®, histological examination, or any combination thereof. In some cases, the improved health of the skin 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 2 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 2 or about 6,000 cells / cm 2 and may further be mixed, if necessary, with one or more pharmaceutically acceptable excipients to prepare a composition. The method according to any one of claims 70 - 72. 【0087】 【0089】The described methods can produce one or more proteins, which may include cytokines, growth factors, membrane-bound signaling molecules, cell adhesion molecules, protective proteins, immune proteins, and extracellular matrix proteins, intracellular signaling molecules, metabolite exchange enzymes, protein-modulating enzymes ( / proteases), protein-binding modulators / protease inhibitors, scaffold / adapter proteins, structural proteins, transport proteins or carrier proteins, transmembrane signaling receptors, 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, cell development processes (e.g., cell differentiation or morphogenesis of cell components), cellular metabolic processes, cellular responses to stimuli, cell export, 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, anatomical structure morphogenesis, cell development processes, growth, etc.), proliferation, immune system processes (e.g., immune effector processes, immune responses, immune system development, leukocyte activation, leukocyte migration, etc.), localization Cellular localization (e.g., cellular localization, establishment of localization, cellular localization, macromolecule localization, etc.), mobility (e.g., cell motility, taxis, etc.), metabolic processes (e.g., biosynthetic 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.), and 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 produces one or more proteins containing 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 another example, the method produces one or more proteins containing 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 yet another example, the method produces one or more proteins containing CSF1, CXCL12, DKK1, GDF15, HGF, IL6, PDGFB, TGFB1, TIMP1, or a combination thereof. In yet another example, the method produces one or more proteins containing ANG, CSTB, NAP1L4, Toll-like receptor 3 (TLR3), or a combination thereof. In another example, this 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 produces one or more proteins including ANG, decorin (DCN), baculovirus IAP repeat-containing protein 2 (BIRC2), platelet-derived growth factor subunit B (PDGFB), or a combination thereof. In yet another example, the method produces one or more proteins including a tissue inhibitor of metalloproteinase 4 (TIMP4), CRIM1, Unc-5 netrin receptor C (UNC5C), a tissue inhibitor of metalloproteinase 2 (TIMP2), or a combination thereof. In another example, this 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 one or more proteins including UNC5C, TLR3, plasminogen activator, urokinase receptor (PLAUR), glycoprotein Ib platelet subunit alpha (GP1BA), SDC4, thrombomodulin (THBD), IL7R, TF, or a combination thereof. In yet 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, 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 TNFRSF21. In yet another example, the method produces one or more proteins containing TNFRSF21, GP1BA, 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 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, 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, 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 another example, the method produces one or more proteins including XCL1, CCL5, CCL20, CCL4, CXCL5, PTX3, CCL13, IFNL1, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, CXCL1, or combinations thereof.

[0098] 【0100】In another example, the method produces one or more proteins containing GP1BA. In another example, the method produces one or more proteins containing TNFRSF21, SEMA7A, or a combination thereof. In another example, the method produces one or more proteins containing UNC5C, FSTL1, TNFRSF21, FST, MET, BSG, THBS1, FLT1, FSTL3, SEMA7A, or a combination thereof. In another example, the method produces one or more proteins containing 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, the method produces 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. In yet another example, the method produces one or more proteins containing insulin (INS). In yet another example, the method produces one or more proteins containing IL6, IL21, or a combination thereof. In yet another example, the method produces one or more proteins containing platelet-derived growth factor beta (PDGFβ). In yet another example, the method produces one or more proteins containing SEREPIN1, PLAUR, MMP1, or a combination thereof. In yet another example, the method produces one or more proteins containing β2-microglobulin (B2M).

[0100] 【0102】In another example, this method produces one or more proteins containing TGFβ1, GDF15, or a combination thereof. In yet another example, this method produces one or more proteins containing Toll-like receptor 3 (TLR3). In yet another example, this method produces one or more proteins containing follistatin-like receptor 1 (FSTL1). In yet another example, this method produces one or more proteins containing IGFBP3, SEREPINE1, FAS, THBS1, or a combination thereof. In yet another example, this 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】The following compositions are provided herein: a) a secretome in an amount of approximately 0.1 w / w% or more 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. 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 is useful for inducing biased expression in the placenta. A method is provided herein comprising the step of administering any of these compositions to a subject requiring administration of the composition, wherein the composition induces chemokine activity in the subject. The use of any of these compositions for treating a subject requiring treatment is provided herein. The use of any of these compositions for manufacturing a pharmacopoeia for treating a subject requiring treatment is provided herein.

[0103] 【0105】Compositions comprising a) 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. 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. The use of any of these compositions for treating a subject requiring it is also provided herein. Uses of any of such compositions for manufacturing pharmaceuticals for treating subjects that require them are provided herein.

[0104] 【0106】 A composition comprising a) about 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. 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 such compositions is useful for inducing broad endometrial expression. A method comprising the step of administering any of such compositions to a subject requiring administration of the composition is provided herein. 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.

[0105] 【0107】A composition comprising a) about 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. 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 comprising the step of administering any of such compositions to a subject requiring administration of the composition is provided herein. 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】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, CXCL5, PF4, or a 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, CXCL5, and PF4. In another example, the secretome comprises CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, 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 that can be treated 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 that can be treated with chemokines.

[0107] 【0109】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 CSF1, GDF15, IFNL1, IFNL2, IL21, IL6, MIF, NAMPT, SPP1, TGFB1, TIMP1, or a combination thereof. In one example, 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. In another example, the secretome comprises CSF1, GDF15, IFNL1, IFNL2, IL21, IL6, MIF, NAMPT, SPP1, TGFB1, and TIMP1. Any of these compositions is useful for inducing cytokine activity. A method is provided herein that includes 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 that can be treated with cytokines. 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 that can be treated with cytokines.

[0108] 【0110】Compositions are provided herein that comprise a) a secretome in an amount of approximately 0.1 w / w% or more 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. In one example, the secretome comprises one, two, three, four, five, six, seven, or eight of 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 proliferation. A method is provided herein that comprises the step of administering any of these compositions to a subject requiring administration of the composition. The use of any of such compositions for treating subjects requiring treatment who have a disease or condition treatable with growth factors 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 treatable with growth factors is also provided herein.

[0109] 【0111】Compositions comprising a) 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. 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. Methods for inducing RNA binding activity in a subject requiring induction of RNA binding activity, comprising administering any of such compositions to the subject, are provided herein. Use of any of such compositions for inducing RNA binding activity in a subject requiring induction of RNA binding activity is provided herein. Use of any of such compositions for producing a pharmacopoeia for inducing RNA binding activity in a subject requiring induction of RNA binding activity is provided herein.

[0110] 【0112】The following compositions are provided herein: 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 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. 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】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 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. 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 compositions are 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 these compositions to the subject requiring induction of an immune response.The use of any of such compositions for inducing an immune response in subjects requiring induction of an immune response is provided herein. The use of any of such compositions for manufacturing a pharmaceutical for inducing an immune response in subjects requiring induction of an immune response is also provided herein.

[0112] 【0114】 The following compositions are provided herein: 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 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. 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】The following compositions are provided herein: 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 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 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, and TNFRSF1A, or any combination thereof. In another example, the secretome comprises ANG, B2M, CCL20, KLK3, TLR3, and TNFRSF1A. Any of these compositions may exhibit antibacterial activity. In one example, the secretome includes one or more of CCL4, IFNL1, IFNL2, IL21, IL6, and TLR3, or any combination thereof. In another example, the secretome includes CCL4, IFNL1, IFNL2, IL21, IL6, and TLR3.Any of these compositions may exhibit antiviral activity. Any of these 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 these compositions to the subject requiring such administration. The use of any of these compositions for treating a microbial infection in a subject requiring treatment of a microbial infection is provided herein. The use of any of these compositions for manufacturing a pharmaceutical for treating a microbial infection in a subject requiring treatment of a microbial infection is provided herein.

[0114] 【0116】 Compositions comprising a) 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. 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】Compositions comprising a) 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. 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】Compositions comprising a) 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. In one example, the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelfth, twelfth, and The use of any of such compositions for manufacturing a pharmaceutical for inducing placental development in subjects requiring induction of placental development is provided herein.

[0117] 【0119】Compositions comprising a) 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. 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 also provided, 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 also provided. The use of any of these compositions is provided herein for manufacturing a pharmaceutical for inducing CNS development in subjects requiring induction of CNS development.

[0118] 【0120】Compositions comprising 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 DKK1, FST, TGFB1, FLT1, DKK3, 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 one of such compositions for inducing morphogenesis in subjects requiring morphogenesis induction is provided herein. The use of any of such compositions for manufacturing a pharmaceutical for inducing morphogenesis in subjects requiring morphogenesis induction is provided herein.

[0119] 【0121】A composition comprising a) about 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, 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. A composition comprising 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 includes B2M, IL7R, or a combination thereof. In another example, the secretome contains B2M and IL7R. Such a secretome is 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 yet another example, the secretome contains CTSB, TPP1, and CES1. Such a secretome is useful for inducing the differentiation of stem cells into epithelial cells.

[0120] 【0122】In one example, the secretome comprises MET. Such a secretome is useful for inducing the differentiation of stem cells into neurons. In one example, the secretome comprises CCN1. Such a secretome is useful for inducing the differentiation of stem cells into chondrocytes. In one example, the secretome comprises TGFβ1. Such a secretome is useful for inducing the differentiation of stem cells into chondrocytes. In one example, the secretome comprises LGALS1. Such a secretome is useful for inducing the differentiation of stem cells into myofiform cells. Methods for inducing in vitro, ex vivo, or in vivo cell differentiation in subjects requiring induction of cell differentiation are provided herein, comprising administering any of such compositions. Use of any of such compositions for inducing in vitro, ex vivo, or in vivo cell differentiation in subjects requiring induction of cell differentiation is provided herein. The use of any of such compositions for manufacturing pharmaceuticals for in vitro, ex vivo, or in vivo cell differentiation in subjects requiring induction of cell differentiation is provided herein.

[0121] 【0123】Compositions comprising 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 SIGLEC9, POSTN, 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 producing a medicament for inducing or promoting cell adhesion in subjects requiring induction or promotion of cell adhesion are provided herein.

[0122] 【0124】 Compositions comprising a) approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, 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】Compositions comprising a) approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, 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, the secretome comprises LGALS3 and LGALS1. Methods for inducing or enhancing an extracellular matrix in a subject requiring induction or enhancement of the extracellular matrix are provided herein, comprising the step of administering one of such compositions to a subject requiring induction or enhancement of the extracellular matrix. Use of any of such compositions for inducing or enhancing an extracellular matrix in a subject requiring induction or enhancement of the extracellular matrix, or for producing a pharmacopoeia for inducing or enhancing an extracellular matrix in a subject requiring induction or enhancement of the extracellular matrix, are provided herein.

[0124] 【0126】The following compositions are provided herein: 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 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 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】 Provided herein are compositions comprising a) a secretome of approximately 0.1 w / w% or more and b) a pharmaceutically acceptable excipient, 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. Provided herein are 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 the step of administering one of such compositions to subjects requiring induction or enhancement of the activity of metabolite reciprocating enzymes. The use of any such composition is provided herein for inducing or enhancing the activity of metabolite reciprocating enzymes in subjects requiring induction or enhancement of metabolite reciprocating enzyme activity, or for manufacturing a pharmaceutical for inducing or enhancing the activity of metabolite reciprocating enzymes in subjects requiring induction or enhancement of metabolite reciprocating enzyme activity.

[0126] 【0128】Compositions comprising 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 FAP, LGMN, HGF, CTSB, TPP1, KLK3, furin, 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】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 IGFBP3, TIMP4, FSTL1, BIRC2, FST, SERPINE1, TIMP1, IGFBP2, FSTL3, IGFBP4, 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 includes IGFBP3, TIMP4, FSTL1, BIRC2, FST, SERPINE1, TIMP1, IGFBP2, FSTL3, IGFBP4, and TIMP2. 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 is provided herein, 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. 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 pharmacopoeci 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 is provided herein.

[0128] 【0130】A composition comprising a) about 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises BSG. 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 is provided herein, comprising the step of administering one of such compositions to a subject requiring induction or enhancement of the activity of the scaffold / adapter protein. The use of one of such compositions 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 producing a pharmacopoeia 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 is provided herein.

[0129] 【0131】 A composition comprising a) about 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises NUP85. 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 one of such compositions to a subject requiring induction or enhancement of the activity of a 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 a 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 a structural protein, is provided herein.

[0130] 【0132】Compositions comprising a) approximately 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of ALB, TPP1, LDLR, RBP4, 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 a transport / carrier protein in a subject requiring induction or enhancement of the activity of the transport / carrier protein are also provided herein, comprising the step of administering one of such compositions to a subject requiring induction or enhancement of the activity of the transport / carrier protein. 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】Compositions comprising a) 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. 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】Compositions comprising a) 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, 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 also provided herein, comprising the step of administering one of such compositions to subjects requiring induction of cell adhesion. The use of any such composition for inducing cell adhesion in subjects requiring induction of cell adhesion, or for manufacturing a pharmaceutical for inducing cell adhesion in subjects requiring induction of cell adhesion, is provided herein.

[0133] 【0135】a) A composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, wherein the secretome is XCL1, IGFBP3, TGFβ1, CCL5, TIMP4, CCL20, FSTL1, CCL4, BIRC2, BCL10, CD99, LGALS3, CXCL5, TNFRSF21, FST, SERPINE1, GP1BA, PDGFB, F11R, CCL13, TIMP Compositions comprising one or more of the following, or a combination thereof, are provided herein: 1, 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】Provided herein are compositions comprising a) a secretome in an amount of approximately 0.1 w / w% or more and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of TGFβ1, TNFRSF21, 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. Provided herein are methods for inducing cell proliferation in subjects requiring induction of cell proliferation, comprising the step of administering one of such compositions to subjects requiring induction of cell proliferation. Provided herein are the use of any of such compositions for inducing cell proliferation in subjects requiring induction of cell proliferation, or for producing a pharmacopoeia for inducing cell proliferation in subjects requiring induction of cell proliferation.

[0135] 【0137】The following compositions are provided herein: a) a secretome in an amount of approximately 0.1 w / w% or more and b) a pharmaceutically acceptable excipient, wherein the secretome comprises one or more of UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, 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. A method for inducing cell organization or biodevelopment in a subject requiring induction of cell organization or biodevelopment is provided herein, comprising the step of administering one of such compositions to a subject requiring induction of cell organization or biodevelopment. The use of one of such compositions for inducing cell organization or biodevelopment in a subject requiring induction of cell organization or biodevelopment, or for manufacturing a pharmacopoeia for inducing cell organization or biodevelopment in a subject requiring induction of cell organization or biodevelopment is also provided herein.

[0136] 【0138】a) A composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, 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, GPC1, CCL7, D a. Includes KK3, 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, in which case the secretome induces cell death; e. Includes SEMA7A, in which case the secretome induces cell growth; f. g. UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof, in which case the secretome induces the organization of cellular components; g. UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or a combination thereof, in which case the secretome induces the process of cell development; h. 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. 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 which case 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 combinations thereof, in which case the secretome induces a cellular response to stimulation; l. TNFRSF21, in which case the secretome induces export from the cell; m. TNFRSF21, GP1BA, also Compositions are provided herein that include combinations thereof, in which 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 combinations thereof, in which case the secretome induces cell communication.

[0137] 【0139】a) a composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable 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. TNFRSF Compositions are provided herein that include 21, in which case 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 a combination thereof, in which case the secretome induces signal transduction.

[0138] 【0140】a) a composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, 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. Compositions are provided herein that induce: c. THBS1, in which case the secretome induces 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 cell development processes; or f. SEMA7A, or a combination thereof, in which case the secretome induces proliferation.

[0139] 【0141】a) A composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, 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. Compositions are provided herein that, in this case, the secretome induces an immune response; c. comprising FLT1, in this case the secretome induces immune system development; d. comprising TNFRSF21, in this case the secretome induces leukocyte activation; or e. comprising XCL1, CCL5, CCL20, CCL4, BCL10, CD99, LGALS3, CXCL5, CCL13, CCL8, CXCL11, CCL7, PF4, CCL26, CXCL1, or a combination thereof, in this case the secretome induces leukocyte migration.

[0140] 【0142】a) a composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises a. NUP85, GPC1, or a combination thereof, in which case the secretome induces cellular 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 so d. Including a combination of the following, in which case the secretome induces cell localization; d. Including TNFRSF21, NUP85, GPC1, or a combination thereof, in which case the secretome induces macromolecule localization; e. Including 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. Including 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) a composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, 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, CC Compositions comprising L7, GDF15, CCL26, TIMP2, 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】 The following compositions are provided herein: 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.

[0143] 【0145】Compositions comprising a) approximately 0.1 w / w% or more of secretome and b) pharmaceutically acceptable 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 system processes.

[0144] 【0146】 a) A composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, 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, SEMA7 Compositions are provided herein that comprise A. DKK1, INFRSF10C, 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】Compositions comprising a) about 0.1 w / w% or more of a secretome and b) a pharmaceutically acceptable excipient, 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, are provided herein.

[0146] 【0148】a) a composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, 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 For use when treating; d. containing BIRC2, FAS, TNFRSF1A, INFRSF10C, or a combination thereof, in which case the secretome is intended for use when inducing apoptosis or signaling; e. containing CXCL12, in which case the secretome induces Slit / Robo-mediated axonal guidance; f. containing UNC5C, in which case the secretome induces Netrin-mediated axonal guidance; g. SERPINE1, PLAUR, GP1BA, THBD, KLK3, TF, or a combination thereof Includes a combination, 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. Includes FAS, in which case the secretome induces the FAS signaling pathway; l. Includes TGFβ1, MIF, FST, INS, or a combination thereof In this case, the secretome induces the gonadotropin-releasing hormone receptor pathway; m. Including IL6, CCL5, CCL20, CCL4, CCL13, CCL8, CCL7, PF4, CCL26, or a combination thereof, in this case, the secretome induces inflammation mediated by chemokine or cytokine signaling pathways; n. Including insulin (INS), in this case, the secretome induces the MAPKK / MAPK cascade; o. Including insulin (INS), in this case, the secretome induces the PKB signaling cascade; p.Compositions are provided herein that include IL6, IL21, or a combination thereof, in which case the secretome induces the interleukin signaling pathway; q. PDGFB, in which case the secretome induces the PDGF signaling pathway; r. SEREPIN1, PLAUR, MMP1, or a combination thereof, in which case the secretome induces the plasminogen activation cascade; s. B2M, in which case the 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】 Methods comprising administering any of such compositions to a subject requiring administration of the composition are provided herein. Uses of any of such compositions for treating a subject requiring treatment, or for manufacturing a pharmacopoeia for treating a subject requiring treatment, are provided herein. Uses of any of such compositions for use in in vitro culture or assay are provided herein.

[0148] 【0150】 In any of these compositions, the composition may be substantially cell-free. Alternatively, the composition may be cell-free.

[0149] 【0151】 It may 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.

[0150] 【0152】In any of these embodiments, 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 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, 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 may be present in a ratio of approximately 1:1 to approximately 20:1. For example, each protein may be present in a ratio of approximately 1:1, approximately 2:1, approximately 3:1, approximately 4:1, approximately 5:1, approximately 6:1, approximately 7:1, approximately 8:1, approximately 9:1, approximately 10:1, approximately 11:1, approximately 12:1, approximately 13:1, approximately 14:1, approximately 15:1, approximately 16:1, approximately 17:1, approximately 18:1, approximately 19:1, or approximately 20:1.

[0152] 【0154】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 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 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).

[0154] 【0156】 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.

[0155] 【0157】In some cases, the composition contains protein 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, and 23 ng / ml. It may be included in concentrations of less than 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 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 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.

[0157] 【0159】 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, emulsionosomes, 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), 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, and 25 nm. 100nm or less is also possible. In some cases, nanoparticles are larger than 1 nanometer (nm), larger than 2 nm, larger than 3 nm, larger than 4 nm, larger than 5 nm, larger than 6 nm, larger than 7 nm, larger than 8 nm, larger than 9 nm, larger than 10 nm, larger than 11 nm, larger than 12 nm, larger than 13 nm, larger than 14 nm, larger than 15 nm, larger than 16 nm, larger than 17 nm, larger than 18 nm, larger than 19 nm, larger than 20 nm, larger than 21 nm, larger than 22 nm, larger than 23 nm, larger than 24 nm, and 2 It may be greater than 5nm, 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 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 may be better understood by referring to the following non-limiting examples provided as exemplary embodiments of the Application. These examples are presented to more fully illustrate the embodiments, but should not be construed in any way as limiting the scope of the Application.

[0160] Example 1 Secretome Composition Profile 【0162】The secretome composition was determined from various stem cell culture extracts using the MILLIPLEX MAP Human Cytokine / Chemokine 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 is a colorimetric assay used to determine cell viability by evaluating the metabolic activity of cells. CCD-966SK human dermal fibroblasts derived from ATCC CRL-1881 were grown at 37°C for 48, 72, or 96 hours with 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 used for reading at 595 nm with an ELISA reader, and the results are shown in Figure 3. Skin cell growth was significantly increased at secretome concentrations greater than 2.5% and treatment times of 72 hours or longer. This increased growth suggests that secretome may increase the growth of facial skin cells, thereby potentially mitigating signs of aging such as wrinkles and age spots. Furthermore, the improved growth rate suggests 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】 The Transwell migration assay was used to test the migration response of cells to different inducers and inhibitors. 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). The presence of MCP-1 in the Transwell assay increased the migration of the tested dermal cells, 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 comprises nanoparticles carrying lipids and secretomes and other cosmetically acceptable components. Secretome proteins such as MCP-1, CXCL2, IL-6, 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 activators. 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 can be packaged in a plastic vial. The subject may apply the cream to the face to prevent wrinkles and reduce their presence. Alternatively, inactive ingredients may be added to the formulation to form a liquid. The liquid can be applied to a patch. The patches can be packaged in sealed containers to prevent the cosmetic formulation from drying out. The patches can be applied to the face to prevent age-related wrinkles.

[0164] Example 5 Cosmetic composition having a liposome carrier 【0166】 Cosmetic compositions are formulated using nanoliposome carriers encapsulating secretomes disclosed herein, such as proteins MCP-1, CXCL2, IL-6, IL-8, and VEGF. Nanoliposomes can be formed using the methods described herein. Nanoliposomes can be combined with filler solutions of saline and hyaluronic acid. Additional inactive ingredients may be added to form injectable solutions. Injectable solutions can be packaged in disposable dispensers or delivery tools such as syringes. Medical professionals can treat subjects by intradermal injection containing the nanoliposome composition to reduce the presence of wrinkles.

[0165] 【0167】 Another cosmetic composition is formed by a single-layer liposome carrier encapsulating the secretome disclosed herein. The single-layer liposome may contain secretome proteins, such as MCP-1, CXCL2, IL-6, IL-8, and VEGF. The single-layer liposome may be formed using the method described herein. The single-layer liposome 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 face of the target to reduce the effects of skin aging.

[0166] Example 6 Regenerative medicine 【0168】 The compositions herein are used in regenerative medicines. Pharmaceutical formulations are used with the secretomes disclosed herein, for example, to treat liver failure. Pharmaceutical compositions may be formulated with 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 include pharmaceutically acceptable excipients, such as saline or phosphate buffer. Pharmaceutical compositions can be administered intravenously (IV) to treat liver failure. IV administration may be daily. Secretome proteins may act as regenerative signals in the subject, promoting liver healing. This treatment can, for example, alleviate liver scarring, hepatic fat deposition, cirrhosis, or any combination thereof, and reverse liver failure.

[0167] 【0169】Another pharmaceutical formulation is formulated using the secretome disclosed herein and administered to a subject suffering from a stroke. This pharmaceutical composition may 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 comprises pharmaceutically acceptable excipients, such as saline or a phosphate buffer. The pharmaceutical composition can be administered intravenously after a stroke in the subject. The pharmaceutical composition may also be administered multiple times. The secretome proteins may 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 the stroke.

[0168] 【0170】 Another pharmaceutical formulation is formulated using the secretomes disclosed herein and administered to the subject during surgery. The pharmaceutical composition may be formulated using secretome proteins, e.g., VEGF, EGF, PDGF, MCP-1, CXCL2 (GRO), PDGF (e.g., PDGF-AA), IL-6, IL-8, or any combination thereof. The composition comprises pharmaceutically acceptable excipients, e.g., saline or phosphate buffers. The pharmaceutical composition may be applied to the surgical wound by spray. The 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 trophic membrane Stem cell (hTSC) cell lines (i.e., hTSC cell line 1, hTSC cell line 2, and hTSC cell line 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 2The cells were washed and the culture medium was replaced without supplementation. Hypoxia was induced in the chamber (e.g., cultured in a 2% O2 gas mixture for approximately 24 hours). The culture medium was collected and frozen until use. Culture medium from all three cell lines was 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 Ontology Analysis was used to identify, group, and analyze 104 proteins 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 function and process based on these results are shown in Table 2 below. 【0213】

[0175] 【0214】 [Table 2-1] 【0215】 [Table 2-2] 【0216】 [Table 2-3] 【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】Hypoxia has been found to induce the expression of a number of proteins, and these proteins can be utilized in the secretome as described above. 【0227】 【0177】The secretome is a promising cell-free alternative for cell-based therapies. The secretome is dynamic in its therapeutic effects and can be designed and customized according to the intended uses in oncology, regenerative medicine, and pharmaceutical cosmetics. 【0228】 【0178】Several embodiments are shown and described herein, but such embodiments are provided by way of example only. Without departing from the present invention, numerous variations, modifications, and substitutions can occur. It should be understood that various alternatives to the embodiments of the invention described herein can be employed in practicing the present invention. Form is provided only as an example. Without departing from the present invention, numerous variations, modifications, and substitutions can occur. It should be understood that various alternatives to the embodiments of the invention described herein can be employed in practicing the present invention. Claims at the time of international filing [Section 1] A composition 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. [Section 2] The composition according to claim 1, wherein the secretome further comprises one or more of the proteins CXCL2(GRO), IL-6, IL-8, and VEGF. [Section 3] The composition according to claim 1, wherein the secretome further comprises two of the proteins CXCL2(GRO), IL-6, IL-8, and VEGF. [Section 4] The composition according to claim 1, wherein the secretome further comprises three of the proteins CXCL2(GRO), IL-6, IL-8, and VEGF. [Section 5] The composition according to claim 1, wherein the secretome further comprises all of the CXCL2(GRO), IL-6, IL-8, and VEGF proteins. [Section 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. [Section 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. [Section 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. [Section 9] A composition comprising (a) MCP-1, (b) one or more further proteins selected from IL-6, VEGF, PDGF-AA, IL-8, or CXCL2(GRO); and (c) an excipient acceptable as a pharmaceutical or 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. [Section 10] (a) MCP-1, CXCL2 (GRO), and one or more additional proteins from among IL-8, MCP-3, IL-6, G-CSF, or VEGF; and (b) Excipients that are permitted 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. [Section 11] A composition comprising liposomes containing phospholipids and secretomes, and excipients acceptable as pharmaceuticals or cosmetics, wherein the composition is cell-free. [Section 12] The composition according to claim 11, wherein the secretome is encapsulated in the liposome. [Section 13] The composition according to claim 11 or 12, wherein the liposomes are in the form of nanoparticles. [Section 14] The composition according to claim 13, wherein the nanoparticles have an average particle size of about 10 to about 400 nanometers in diameter. [Section 15] The composition according to claim 14, wherein the nanoparticles have an average particle size of about 50 to about 300 nanometers in diameter. [Section 16] The composition according to claim 15, wherein the nanoparticles have an average particle size of about 100 to about 200 nanometers in diameter. [Section 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. [Section 18] The composition according to any one of claims 11 to 17, wherein the secretome comprises a microvesicle, an exosome, or a combination thereof. [Section 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. [Section 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. [Section 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. [Section 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 proteins CXCL2 (GRO), IL-6, IL-8, and VEGF. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 34] The composition according to claim 22, wherein the secretome comprises MCP-1, CXCL2, IL-6, IL-8, and VEGF proteins. [Section 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. [Section 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. [Section 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. [Section 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. [Section 39] The composition according to claim 34, wherein the secretome further comprises IL-6, the ratio of MCP-1 to IL-6 being in the range of about 30:1 to about 50:1 and / or the ratio of CXCL2 to IL-6 being in the range of about 10:1 to about 20:1. [Section 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. [Section 41] The composition according to claim 35, wherein the secretome further comprises VEGF, the ratio of MCP-1 to VEGF is in the range of about 30:1 to about 50:1, and the ratio of CXCL2 to VEGF is in the range of about 10:1 to about 20:1. [Section 42] The composition according to any prior claim, 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. [Section 43] A composition according to any one of claims 1 to 42, comprising a hydrophilic surfactant. [Section 44] A composition according to any one of claims 1 to 43, comprising a vitamin. [Section 45] A composition according to any one of claims 1 to 44, comprising a hydrophobic surfactant. [Section 46] A composition according to any one of claims 1 to 45, comprising a fatty acid molecule. [Section 47] A composition according to any one of claims 1 to 46, comprising linoleic acid. [Section 48] A composition according to any one of claims 1 to 47, comprising collagen. [Section 49] A composition according to any one of claims 1 to 48, comprising hyaluronic acid. [Section 50] A composition according to any one of claims 1 to 49, which is free of serum, antibiotics, or any combination thereof. [Section 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. [Section 52] A composition according to any one of claims 1 to 51, which is free of color additives. [Section 53] The composition according to any one of claims 1 to 52, which is in the form of 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. [Section 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. [Section 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. [Section 56] The method according to claim 55, for treating a disease or condition in the subject. [Section 57] The method according to claim 55, which provides regenerative medicine. [Section 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). [Section 59] The method according to claim 55, for treating or improving the condition of the skin of the subject. [Section 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. [Section 61] The method according to any one of claims 55 to 60, wherein the subject is a human. [Section 62] Use of the composition according to any one of claims 1 to 54 for the treatment of a subject requiring it. [Section 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. [Section 64] The use according to claim 62 or 63 for treating a disease or condition in the subject. [Section 65] Use according to any one of claims 62 to 64 for regenerative medicine. [Section 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). [Section 67] The use according to any one of claims 62 to 64 for treating or improving the condition of the skin of the subject. [Section 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. [Section 69] The use according to any one of claims 62 to 68, wherein the subject is a human. [Section 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 a 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. [Section 71] Low oxygen is 2% O 2 The method according to claim 70, wherein the gas mixture is induced for approximately 24 hours. [Section 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. [Section 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. [Section 74] The method according to any one of claims 70 to 73, wherein the one or more proteins include CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL15, Pf4, or any combination thereof. [Section 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. [Section 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. [Section 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. [Section 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. [Section 79] The method according to any one of claims 70 to 73, wherein the one or more proteins include CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, PF4, or a combination thereof. [Section 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. [Section 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. [Section 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. [Section 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. [Section 84] The method according to any one of claims 70 to 73, wherein the one or more proteins include 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 103] The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, CCL5, CCL20, CCL28, CCL4, CXCL5, CCL13, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SPP1, CXCL1, or a combination thereof. [Section 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. [Section 105] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise SEMA7A. [Section 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. [Section 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. [Section 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. [Section 109] The method according to any one of claims 70 to 73, wherein the one or more proteins include BSG, NUP85, or LDLR. [Section 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. [Section 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. [Section 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. [Section 113] The method according to any one of claims 70 to 73, wherein the one or more proteins include 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 124] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise TNFRSF21. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 131] 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 137] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise THBS1. [Section 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. [Section 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. [Section 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. [Section 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. [Section 142] 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, FLT1, CCL25, CXCL11, CCL7, PF4, CCL26, SEMA7A, CXCL1, or a combination thereof. [Section 143] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise FLT1. [Section 144] 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, CCL13, CCL8, CXCL11, CCL7, PF4, CCL26, CXCL1, or a combination thereof. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 154] 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. [Section 155] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise FURIN. [Section 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. [Section 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. [Section 158] The method according to any one of claims 70 to 73, wherein the one or more proteins include XCL1, CCL5, CCL20, CCL4, CXCL5, PTX3, CCL13, IFNL1, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, CXCL1, or a combination thereof. [Section 159] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise GP1BA. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 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. [Section 170] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise CXCL12. [Section 171] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise UNC5C. [Section 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. [Section 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. [Section 174] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise FSTL1. [Section 175] The method according to any one of claims 70 to 73, wherein the one or more proteins mentioned above include FAS. [Section 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. [Section 177] The method according to any one of claims 70 to 73, wherein the one or more proteins include IL6, CCL5, CCL20, CCL4, CCL13, CCL8, CCL7, PF4, CCL26, or a combination thereof. [Section 178] The method according to any one of claims 70 to 73, wherein the one or more proteins include insulin (INS). [Section 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. [Section 180] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise platelet-derived growth factor beta (PDGFβ). [Section 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. [Section 182] The method according to any one of claims 70 to 73, wherein the one or more proteins include β2-microglobulin (B2M). [Section 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. [Section 184] The method according to any one of claims 70 to 73, wherein the one or more proteins include Toll-like receptor 3 (TLR3). [Section 185] The method according to any one of claims 70 to 73, wherein the one or more proteins include follistatin-like 1 (FSTL1). [Section 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. [Section 187] The method according to any one of claims 70 to 73, wherein the one or more proteins comprise F11R. [Section 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. [Section 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. [Section 190] The composition according to claim 189, which is substantially free of cells or contains no cells. [Section 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, twelve, thirteen, or fourteen of CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL15, and PF4. [Section 192] The composition according to claim 189 or 190, wherein the secretome comprises CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL15, and PF4. [Section 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. [Section 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. [Section 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. [Section 196] Use of the composition according to any one of claims 189 to 193 for the manufacture of a pharmacopoeia for treating a subject requiring induction of chemokine activity, wherein the composition induces chemokine activity in the subject. [Section 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. [Section 198] The composition according to claim 197, which is substantially free of cells or contains no cells. [Section 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. [Section 200] The composition according to claim 197 or 198, wherein the secretome comprises SPP1, DKK1, SERPINE1, FLT1, FSTL3, MATN3, PAPPA, GDF15, HGF, and IGFBP3. [Section 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. [Section 202] The composition according to any one of claims 197 to 201, wherein the secretome exhibits biased expression in the placenta. [Section 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. [Section 204] Use of the composition according to any one of claims 197 to 202 for treating an object requiring treatment. [Section 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. [Section 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. [Section 207] The composition according to claim 206, which is substantially free of cells or contains no cells. [Section 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. [Section 209] The composition according to claim 206 or 207, wherein the secretome comprises FST, NID1, MET, TGFBI, FSTL1, NID2, CRIM1, and PDGFB. [Section 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. [Section 211] The composition according to any one of claims 206 to 210, wherein the secretome exhibits broad expression in the placenta. [Section 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. [Section 213] Use of the composition according to any one of claims 206 to 211 for treating an object requiring treatment. [Section 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. [Section 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. [Section 216] The composition according to claim 215, which is substantially free of cells or contains no cells. [Section 217] The composition according to claim 215 or 216, wherein the secretome comprises one or two of CXCL12, LGALS1, and ADAMTSL1. [Section 218] The composition according to claim 217, wherein the secretome comprises CXCL12, LGALS1, and ADAMTSL1. [Section 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. [Section 220] The composition according to any one of claims 215 to 219, wherein the secretome exhibits broad endometrial expression. [Section 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. [Section 222] Use of the composition according to any one of claims 217 to 220 for treating an object requiring treatment. [Section 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. [Section 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. [Section 225] The composition according to claim 224, which is substantially free of cells or contains no cells. [Section 226] The composition according to claim 224 or 225, wherein the secretome comprises FAP or IGFBP3. [Section 227] The composition according to claim 224 or 225, wherein the secretome comprises FAP and IGFBP3. [Section 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. [Section 229] The composition according to any one of claims 224 to 228, wherein the secretome exhibits biased endometrial expression. [Section 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. [Section 231] Use of the composition according to any one of claims 224 to 229 for treating an object that requires treatment. [Section 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. [Section 233] 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, CXCL5, PF4, or a combination thereof. [Section 234] The composition according to claim 233, which is substantially free of cells or contains no cells. [Section 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, twelve, thirteen, or fourteen of CCL13, CCL20, CCL25, CCL26, CCL28, CCL4, CCL5, CCL7, CCL8, CXCL1, CXCL11, CXCL12, CXCL14, CXCL5, and PF4. [Section 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. [Section 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. [Section 238] A composition according to any one of claims 233 to 237, exhibiting chemokine activity. [Section 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. [Section 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. [Section 241] Use of the composition according to any one of claims 233 to 238 for the manufacture of a pharmacopoeia for treating a subject in need of treatment having a disease or condition that can be treated with chemokines. [Section 242] 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 CSF1, GDF15, IFNL1, IFNL2, IL21, IL6, MIF, NAMPT, SPP1, TGFB1, TIMP1, or a combination thereof. [Section 243] The composition according to claim 22, which is substantially free of cells or contains no cells. [Section 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. [Section 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. [Section 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. [Section 247] A composition according to any one of claims 242 to 246, which exhibits cytokine activity. [Section 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. [Section 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. [Section 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. [Section 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. [Section 252] The composition according to claim 251, which is substantially free of cells or contains no cells. [Section 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. [Section 254] The composition according to claim 251 or 252, wherein the secretome comprises CSF1, CXCL12, DKK1, GDF15, HGF, IL6, PDGFB, TGFB1, and TIMP1. [Section 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. [Section 256] A composition according to any one of claims 251 to 255, comprising the growth factor secretome. [Section 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. [Section 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. [Section 259] Use of the composition according to any one of claims 251 to 256 for the manufacture of a pharmacopoeia for treating a subject in need of treatment having a disease or condition that can be treated with a growth factor. [Section 260] 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 ANG, CSTB, NAP1L4, TLR3, or a combination thereof. [Section 261] The composition according to claim 260, which is substantially free of cells or contains no cells. [Section 262] The composition according to claim 260 or 261, wherein the secretome comprises one, two, or three of ANG, CSTB, NAP1L4, and TLR3. [Section 263] The composition according to claim 262 or 261, wherein the secretome comprises ANG, CSTB, NAP1L4, and TLR3. [Section 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. [Section 265] A composition according to any one of claims 260 to 264, which induces RNA binding activity. [Section 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. [Section 267] Use of the composition according to any one of claims 260 to 265 for inducing RNA binding activity in a subject requiring induction of RNA binding activity. [Section 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. [Section 269] 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 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. [Section 270] The composition according to claim 269, which is substantially free of cells or contains no cells. [Section 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 [Section 272] The composition according to claim 269 or 270, wherein the secretome comprises ADAMTSL1, DCN, FURIN, LUM, MATN3, MMP1, NID1, NID2, PDGFB, POSTN, PTX3, SERPINE, SPP1, TGFβI, THBS1, TIMP1, TIMP2, CCN1, LUM, MATN3, and POSTN. [Section 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. [Section 274] A composition according to any one of claims 269 to 273, which induces extracellular matrix organization. [Section 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. [Section 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. [Section 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. [Section 278] 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 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. [Section 279] The composition according to claim 278, which is substantially free of cells or contains no cells. [Section 280] The aforementioned 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, ten, 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. [Section 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. [Section 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. [Section 283] A composition according to any one of claims 268 to 282, which induces an immune response. [Section 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. [Section 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. [Section 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 subjects requiring induction of an immune response. [Section 287] 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, 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. [Section 288] The composition according to claim 287, which is substantially free of cells or contains no cells. [Section 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 [Section 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. [Section 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. [Section 292] A composition according to any one of claims 287 to 291 for use in treating inflammation. [Section 293] A method for treating inflammation in a subject requiring treatment of inflammation, comprising the step of administering a composition according to any one of claims 287 to 292 to the subject requiring administration of the composition. [Section 294] Use of the composition according to any one of claims 287 to 292 for treating inflammation in a subject requiring treatment of inflammation. [Section 295] Use of the composition according to any one of claims 287 to 292 for the manufacture of a pharmaceutical for treating inflammation in a subject requiring treatment of inflammation. [Section 296] 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 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. [Section 297] The composition according to claim 296, which is substantially free of cells or contains no cells. [Section 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 [Section 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. [Section 300] The composition according to any one of claims 296 to 299, which is antibacterial. [Section 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. [Section 302] The composition according to claim 296 or 297, wherein the secretome comprises ANG, B2M, CCL20, KLK3, TLR3, and TNFRSF1A. [Section 303] The composition according to claim 301 or 302, which is antibacterial. [Section 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. [Section 305] The composition according to claim 296 or 297, wherein the secretome comprises CCL4, IFNL1, IFNL2, IL21, IL6, and TLR3. [Section 306] The composition according to claim 304 or 305, which is antiviral. [Section 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. [Section 308] A composition according to any one of claims 296 to 307 for use in treating microbial infections. [Section 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. [Section 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. [Section 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. [Section 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. [Section 313] The composition according to claim 312, which is substantially free of cells or contains no cells. [Section 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. [Section 315] The composition according to claim 312 or 313, wherein the secretome comprises DCN, POSTN, SDC4, GRN, PAPPA, and TIMP1. [Section 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. [Section 317] A composition useful for wound healing, according to any one of claims 312 to 315. [Section 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. [Section 319] Use of the composition according to any one of claims 312 to 317 for wound healing in subjects requiring wound healing. [Section 320] Use of the composition according to any one of claims 312 to 317 for the manufacture of a medicament for wound healing in subjects requiring wound healing. [Section 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. [Section 322] The composition according to claim 321, which is substantially free of cells or contains no cells. [Section 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. [Section 324] The composition according to claim 321 or 322, wherein the secretome comprises ANGPT1, FLT1, MET, CST3, DKK3, RBP4, and BSG. [Section 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. [Section 326] A composition according to any one of claims 321 to 325, which is useful for inducing embryonic development. [Section 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. [Section 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. [Section 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. [Section 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. [Section 331] The composition according to claim 330, which is substantially free of cells or contains no cells. [Section 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, ten, eleven, twelve, thirteen, or fourteen of ANG, DCN, BIRC2, and PDGFB. [Section 333] The composition according to claim 330 or 331, wherein the secretome comprises ANG, DCN, BIRC2, and PDGFB. [Section 334] The composition according to any one of claims 330 to 333, 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. [Section 335] A composition according to any one of claims 330 to 334, which is useful for inducing placental development. [Section 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. [Section 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. [Section 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. [Section 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. [Section 340] The composition according to claim 339, which is substantially free of cells or contains no cells. [Section 341] The composition according to claim 339 or 340, wherein the secretome comprises one, two, or three of TIMP4, CRIM1, UNC5C, and TIMP2. [Section 342] The composition according to claim 339 or 340, wherein the secretome comprises TIMP4, CRIM1, UNC5C, and TIMP2. [Section 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. [Section 344] A composition according to any one of claims 339 to 343, which is useful for inducing central nervous system (CNS) development. [Section 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. [Section 346] Use of the composition according to any one of claims 339 to 344 for inducing CNS development in subjects requiring induction of CNS development. [Section 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. [Section 348] 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 DKK1, FST, TGFB1, FLT1, DKK3, CCN1, or a combination thereof. [Section 349] The composition according to claim 348, which is substantially free of cells or contains no cells. [Section 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. [Section 351] The composition according to claim 348 or 349, wherein the secretome comprises DKK1, FST, TGFB1, FLT1, DKK3, and CCN1. [Section 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. [Section 353] A composition according to any one of claims 348 to 352, which is useful for inducing morphogenesis. [Section 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. [Section 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. [Section 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. [Section 357] 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 NAP1L4, SPP1, ANGPT1, FST, MET, CTSB, FSTL1, LGALS1, TPP1, OSCAR, CCN1, IGFBP3, TGFB1, B2M, IL7R, CES1, CSF1, or any combination thereof. [Section 358] The composition according to claim 357, which is substantially free of cells or contains no cells. [Section 359] The composition according to claim 357 or 358, wherein the secretome comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelfth, ten [Section 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. [Section 361] The composition according to any one of claims 357 to 360, wherein the secretome induces the differentiation of stem cells. [Section 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. [Section 363] The composition according to claim 362, wherein the secretome comprises SPP1, OSCAR, CCN1, and IGFBP3. [Section 364] The composition according to claim 362 or 363, which induces the differentiation of stem cells into osteoblasts. [Section 365] The composition according to claim 357 or 358, wherein the secretome comprises CSF1. [Section 366] The composition according to claim 364, which induces the differentiation of stem cells into osteoclasts or macrophages. [Section 367] The composition according to claim 357 or 358, wherein the secretome comprises B2M, IL7R, or a combination thereof. [Section 368] The composition according to claim 357 or 358, wherein the secretome comprises B2M and IL7R. [Section 369] The composition according to claim 367 or 368, which induces the differentiation of stem cells into T cells. [Section 370] The composition according to claim 357 or 358, wherein the secretome comprises one or more of CTSB, TPP1, CES1, or any combination thereof. [Section 371] The composition according to claim 370, wherein the secretome comprises CTSB, TPP1, and CES1. [Section 372] The composition according to claim 370 or 371, which induces differentiation of stem cells into epithelial cells. [Section 373] The composition according to claim 357 or 358, wherein the secretome comprises MET. [Section 374] The composition according to claim 373, which induces the differentiation of stem cells into nerve cells. [Section 375] The composition according to claim 357 or 358, wherein the secretome comprises CCN1. [Section 376] The composition according to claim 375, which induces the differentiation of stem cells into chondrocytes. [Section 377] The composition according to claim 357 or 358, wherein the secretome comprises TGFβ1. [Section 378] The composition according to claim 377, which induces the differentiation of stem cells into chondrocytes. [Section 379] The composition according to claim 357 or 358, wherein the secretome comprises LGALS1. [Section 380] The composition according to claim 379, which induces the differentiation of stem cells into myoblasts. [Section 381] The composition according to any one of claims 357 to 380, 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. [Section 382] A method for inducing cell differentiation in vitro, ex vivo, or in vivo in a subject requiring induction of cell differentiation, comprising the step of administering a composition according to any one of claims 357 to 381. [Section 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. [Section 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. [Section 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. [Section 386] The composition according to claim 385, which is substantially free of cells or contains no cells. [Section 387] The composition according to claim 385 or 386, wherein the secretome comprises one or two of SIGLEC9, POSTN, and TGFβI. [Section 388] The composition according to claim 385 or 386, wherein the secretome comprises SIGLEC9, POSTN, and TGFβI. [Section 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. [Section 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. [Section 391] Use of the composition according to any one of claims 385 to 389 for inducing or promoting cell adhesion in subjects requiring induction or promotion of cell adhesion, or for the manufacture of a pharmaceutical for inducing or promoting cell adhesion in subjects requiring induction or promotion of cell adhesion. [Section 392] 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 OSCAR, B2M, or a combination thereof. [Section 393] The composition according to claim 392, which is substantially free of cells or contains no cells. [Section 394] The composition according to claim 392 or 393, wherein the secretome comprises OSCAR or B2M. [Section 395] The composition according to claim 392 or 393, wherein the secretome comprises OSCAR and B2M. [Section 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. [Section 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. [Section 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. [Section 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. [Section 400] The composition according to claim 399, which is substantially free of cells or contains no cells. [Section 401] The composition according to claim 399 or 400, wherein the secretome comprises LGALS3 or LGALS1. [Section 402] The composition according to claim 399 or 400, wherein the secretome comprises LGALS3 and LGALS1. [Section 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. [Section 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. [Section 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. [Section 406] 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 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. [Section 407] The composition according to claim 406, which is substantially free of cells or contains no cells. [Section 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 [Section 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. [Section 410] The composition according to claim 406 or 407, wherein the secretome comprises 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. [Section 411] The composition according to claim 406 or 407, wherein the secretome comprises cytokine activity, and the secretome comprises XCL1, CCL5, CCL20, CCL28, CCL4, CXCL5, CCL13, CCL8, CCL25, CXCL11, CCL7, PF4, CCL26, SPP1, and CXCL1. [Section 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. [Section 413] The composition according to claim 406 or 407, wherein the secretome contains growth factor activity, and the secretome comprises TGFβI, PDGFB, and GDF15. [Section 414] The composition according to claim 406 or 407, wherein the secretome comprises a signal transduction molecule, and the secretome comprises SEMA7A. [Section 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. [Section 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. [Section 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. [Section 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. [Section 419] The composition according to claim 418, which is substantially free of cells or contains no cells. [Section 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. [Section 421] The composition according to claim 418 or 419, wherein the secretome comprises CES1, FAS, MIF, NAMPT, and SPP1. [Section 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. [Section 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. [Section 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. [Section 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. [Section 426] The composition according to claim 425, which is substantially free of cells or contains no cells. [Section 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. [Section 428] The composition according to claim 425 or 426, wherein the secretome comprises FAP, LGMN, HGF, CTSB, TPP1, KLK3, FURIN, and MMP1. [Section 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. [Section 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 the step of administering a composition according to any one of claims 425 to 429 to a subject requiring administration of the composition. [Section 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. [Section 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. [Section 433] The composition according to claim 432, which is substantially free of cells or contains no cells. [Section 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. [Section 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. [Section 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. [Section 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. [Section 438] Use of the composition according to any one of claims 432 to 437 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 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 a protein-binding modulator / protease inhibitor. [Section 439] a) A composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, wherein the secretome contains BSG. [Section 440] The composition according to claim 439, which is substantially free of cells or contains no cells. [Section 441] The composition according to claim 439 or 440, 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. [Section 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. [Section 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. [Section 444] a) A composition comprising approximately 0.1 w / w% or more of secretome and b) a pharmaceutically acceptable excipient, wherein the secretome comprises NUP85. [Section 445] The composition according to claim 444, which is substantially free of cells or contains no cells. [Section 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. [Section 447] 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 a composition according to any one of claims 444 to 446 to a subject requiring administration of the composition. [Section 448] Use of the composition according to any one of claims 444 to 446 for inducing or enhancing the activity of a structural protein in a subject requiring induction or enhancement of the activity of a structural protein, or for the manufacture of a pharmaceutical for inducing or enhancing the activity of a structural protein in a subject requiring induction or enhancement of the activity of a structural protein. [Section 449] 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 ALB, TPP1, LDLR, RBP4, TF, or a combination thereof. [Section 450] The composition according to claim 449, which is substantially free of cells or contains no cells. [Section 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. [Section 452] The composition according to any one of claims 449 to 451, wherein the secretome comprises LDLR. [Section 453] The composition according to claim 449 or 450, wherein the secretome comprises ALB, TPP1, LDLR, RBP4, and TF. [Section 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. [Section 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. [Section 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 pharmaceutical for inducing or enhancing the activity of transport / carrier proteins in subjects requiring induction or enhancement of transport / carrier protein activity. [Section 457] 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 UNC5C, TLR3, PLAUR, GP1BA, SDC4, THBD, IL7R, TF, or a combination thereof. [Section 458] The composition according to claim 457, which is substantially free of cells or contains no cells. [Section 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. [Section 460] The composition according to claim 457 or 458, wherein the secretome comprises UNC5C, TLR3, PLAUR, GP1BA, SDC4, THBD, IL7R, and TF. [Section 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. [Section 462] A method for inducing or enhancing the activity of a transmembrane signaling receptor in a subject requiring induction or enhancement of the activity of a transmembrane signaling 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. [Section 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. [Section 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. [Section 465] The composition according to claim 464, which is substantially free of cells or contains no cells. [Section 466] The composition according to claim 464 or 465, wherein the secretome comprises one, two, three, four, five, or six of SIGLEC9, CD99, TNFRSF21, GP1BA, BSG, POSTN, and TGFβI. [Section 467] The composition according to claim 464 or 465, wherein the secretome comprises SIGLEC9, CD99, TNFRSF21, GP1BA, BSG, POSTN, and TGFβI. [Section 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. [Section 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. [Section 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. [Section 471] 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 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. [Section 472] The composition according to claim 471, which is substantially free of cells or contains no cells. [Section 473] The secretomes mentioned above 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, IGFBP6, THBS1, CCL25, IGFBP2, FSTL3, IGFBP4, KLK3, CXCL11, GPC1, CCL7, DKK3, PF The composition according to claim 471 or 472, comprising one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve [Section 474] The composition according to claim 471 or 472, wherein the secretome comprises 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. [Section 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. [Section 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. [Section 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. [Section 478] 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 TGFβ1, TNFRSF21, PDGFB, or a combination thereof. [Section 479] The composition according to claim 478, which is substantially free of cells or contains no cells. [Section 480] The composition according to claim 478 or 479, wherein the secretome comprises one or two of TGFβ1, TNFRSF21, and PDGFB. [Section 481] The composition according to claim 478 or 479, wherein the secretome comprises TGFβ1, TNFRSF21, and PDGFB. [Section 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. [Section 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. [Section 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. [Section 485] 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, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, MMP1, or a combination thereof. [Section 486] The composition according to claim 485, which is substantially free of cells or contains no cells. [Section 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. [Section 488] The composition according to claim 485 or 486, wherein the secretome comprises UNC5C, BIRC2, LGALS3, BSG, POSTN, TGFβI, SEMA7A, and MMP1. [Section 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. [Section 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. [Section 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 for inducing cell organization or biodevelopment in subjects requiring induction of cell organization or biodevelopment. [Section 492] a) comprising approximately 0.1 w / w% or more of secretome and b) an excipient that is acceptable as a pharmaceutical, 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 cell 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 any combination thereof, the secretome induces cell development processes; h.UNC5C, FSTL1, FST, MET, F11R, BSG, FLT1, FSTL3, SEMA7A, or any 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 s...

Claims

[Claim 1] A composition comprising: 1) 0.625 w / w% or more of human trophoblast stem cell (hTSC) secretome; 2) vitamin B3 or vitamin A; and 3) an excipient acceptable as a pharmaceutical or cosmetic, The hTSC secretome comprises monocyte chemotactic protein 1 (MCP-1), CXCL2 (GRO), interleukin 6 (IL-6), PDGF-AA, IL-8, MCP-3, and vascular endothelial growth factor (VEGF); MCP-1 is present in the composition at a concentration of at least 100 ng / ml; The composition does not contain cells; A composition is formulated to be delivered via nanoparticles, or comprises a nanoliposome carrier. [Claim 2] The composition according to claim 1, wherein the hTSC 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. [Claim 3] The composition according to claim 1, wherein the hTSC secretome is present in the composition in an amount of 2.5% to 10% by weight. [Claim 4] The composition according to claim 1, wherein the nanoparticles have an average particle size of 10 to 400 nanometers in diameter. [Claim 5] The composition according to claim 1, wherein the nanoparticles have an average particle size of 50 to 300 nanometers in diameter. [Claim 6] The composition according to claim 1, wherein the nanoparticles have an average particle size of 100 to 200 nanometers in diameter. [Claim 7] The composition according to claim 1, wherein the hTSC secretome comprises microvesicles, exosomes, or a combination thereof. [Claim 8] The composition according to claim 1, further comprising one or more proteins selected from IP-10, eotaxin, Flt-3L, GM-CSF, macrophage inflammatory protein 1-alpha (MIP-1α), macrophage inflammatory protein 1-beta (MIP-1β), interleukin (IL)-1α, interleukin-1 receptor antagonist (IL-1RA), IL-4, IL-7, IL-10, IL-12P40, IL-13, IL-15, IL-17A, CCL5 (RANTES), macrophage-derived chemokine (MDC), IL-12P70, interferon-alpha (IFN-α), IFN receptor (IFNR), PDGF-AB / BB, or epidermal growth factor (EGF). [Claim 9] The composition according to claim 1, further comprising a hydrophilic surfactant. [Claim 10] The composition according to claim 1, further comprising a hydrophobic surfactant. [Claim 11] The composition according to claim 1, further comprising fatty acid molecules. [Claim 12] The composition according to claim 1, further comprising linoleic acid. [Claim 13] The composition according to claim 1, further comprising collagen. [Claim 14] The composition according to claim 1, further comprising hyaluronic acid. [Claim 15] The composition according to claim 1, which does not contain serum, antibiotics, or a combination thereof. [Claim 16] The composition according to claim 1, which does not contain steroids, cholesterol, choline hydrochloride, hypoxanthine sodium salt, thymidine, putrescine dihydrochloride, ferric nitrate, L-glutamine, or any combination thereof. [Claim 17] The composition according to claim 1, which is in the form of 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. [Claim 18] The composition according to claim 1, 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 a salt thereof, polyethylene glycol, silicone, or any combination thereof. [Claim 19] The composition according to claim 1, wherein the ratio of MCP-1 to CXCL2 (GRO) is in the range of 1:1 to 4:1; the ratio of MCP-1 to IL-6 is in the range of 2:1 to 3:1 or by weight ratio of 3:1 to 4:1; the ratio of MCP-1 to IL-8 is in the range of 4:1 to 6:1; the ratio of MCP-1 to VEGF is in the range of 4:1 to 6:1 or by weight ratio of 7:1 to 9:1; or any combination thereof. [Claim 20] A composition according to any one of claims 1 to 19, for use in treating a skin condition in an object requiring such treatment.

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