Methods and compositions for developing target specific exosome and growth factor products

Abstract

To provide pharmaceutical compositions to treat skin disorders, hair loss, pain, rheumatoid arthritis, osteoporosis, autism, depression, biopolar disorder, anxiety, celiac disease, and cancer.SOLUTION: A pharmaceutical composition comprises a bone marrow-derived secretome composition including at least one component selected from platelet-derived growth factor receptor-b (PDGFRb), insulin-like growth factor binding protein 4 (IGFBP-4), tissue inhibitor of metalloproteinase 2 (TIMP-2), tissue inhibitor of metalloproteinase 1 (TIMP-1), activin A, intercellular adhesion molecule 1 (ICAM-2), ectodysplasin receptor (XEDAR), osteopontin (OPN), tumor necrosis factor receptor 1 (TNF R1), and the like.SELECTED DRAWING: None

Description

[Background technology]

[0001] This application is a continuation of U.S. Provisional Application No. 62 / 798,908, filed January 30, 2019. The benefit of which is claimed and is incorporated herein by reference in its entirety.

[0002] Humans share 99.9% of the same genetic characteristics, and the differences between humans are due to their individual genes. The small differences are contained in single nucleotide polymorphisms (SNPs). Between 6 and 20 of these SNPs are associated with race, ethnicity, skin color, skin type, eye color, and It is presumed that this is responsible for all of the observed differences in cerebral palsy and hair color as well as alopecia. Recent studies have shown that highly specific SNP profiles can determine who develops a disease or condition. who has the disease or condition and who does not, as well as who has the disease or condition They found that the effects of sex on mood and sexual orientation were predictive of the likelihood of developing a sexual orientation disorder. This was true for both men and women.

[0003] Currently, there are few, if any, products that are specific to a particular skin color or ethnicity. Similarly, there are no hair products that address the genetic factors, if any, that cause grey hair or alopecia. Similarly, few products exist that address the genetic basis associated with many diseases or conditions. Therefore, conventional skin and hair products and treatments are based on the recipe. These methods do not adequately address the biological differences found in study subjects.

[0004] Therefore, what is needed is a person's skin color, hair color, alopecia, as well as a person's national or local identity. New dermatological and cosmetic treatments that are ethnicity specific, methods of administering such treatments, and methods of treating The study was carried out to identify mesenchymal stem cells (MSCs), keratinocytes, or melanocytes from representative donors. The target SNPs are included in the DNA of the target gene. Summary of the Invention

[0005] Alopecia, atopic dermatitis, autism spectrum disorder, multiple sclerosis, chronic pain, depression Disease, anxiety, bipolar disorder, osteoporosis, rheumatoid arthritis, celiac disease, type II diabetes, coronary artery US20130232633A1 - Mesenchymal stem cells and methods for treating chronic heart disease, hypertension, multiple complex diseases and / or cancer - Google Patents and methods and compositions relating to exosome therapeutic compositions and methods of their use. It will be disclosed.

[0006] In one embodiment, the present invention relates to a method for treating a disease or disorder in a subject (e.g., alopecia, atopic dermatitis, autism, etc.). dementia spectrum disorder, multiple sclerosis, chronic pain, depression, anxiety, bipolar disorder, osteoporosis, Rheumatoid arthritis, celiac disease, type II diabetes, coronary heart disease, hypertension, multiple complex diseases to treat, inhibit, reduce, ameliorate, prevent, and / or reverse a disease, such as a cancer, Disclosed herein are methods for producing mesenchymal stem cell and exosome therapeutic compositions for The method includes: a) identifying the end user's hair, skin color, skin type, race, or ethnicity; and b) determining whether a single nucleotide polymorphism (SNP) is associated with a disease or disorder in the subject. and c) to identify individuals with the same hair type, color, and / or ethnicity as the subject, but without Single nucleotide polymorphism (SNP) profiles that indicate that a patient will never experience a disease or disorder obtaining mesenchymal stem cells (MSCs) from a targeted donor having a specific profile; and d) and preparing an MSC and exosome preparation from the obtained MSCs. and the exosome preparation comprises and / or contains a corrective SNP and a cytokine. MSCs secreting exosomes were generated in a medium containing sufficient growth conditions to generate MSCs and exosomes that secrete MSCs. In some embodiments, the method comprises culturing MSCs and endometrioids. Characterize exosomal RNA through methods such as sequencing of exosome preparations and to identify the type and amount of growth factors in the cells (proteomic analysis). Including etc.

[0007] The disease or disorder (e.g., alopecia, atopic dermatitis) in a subject of any preceding aspect. , autism spectrum disorder, multiple sclerosis, chronic pain, depression, anxiety, bipolar disorder, osteoporosis Osteopathy, rheumatoid arthritis, celiac disease, type II diabetes, coronary heart disease, hypertension, multiple myelopathy Treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease, disorder, or condition (e.g., a cancer, a genetic disorder, or a genetic disorder) Also disclosed are methods for making mesenchymal stem cell and exosome therapeutic compositions for , SNPs include interleukin 18 (IL-18) (e.g., rs1946518 and / or rs187238, etc.), androgen receptor (AR) (e.g., Rs6152 , Rs2223841, and / or Rs2497938), histone deacetylase (HDAC)-4 (HDAC4) (e.g., Rs9287638), HDAC9 (e.g. For example, Rs2073963 and / or Rs2180439), paired boxes 1(PAX1) (e.g., Rs1160312 and / or Rs6047844) , Forkhead box A2 (FOXA2) (e.g., Rs1160312 and / or or Rs6047844), TAR DNA-binding proteins (TARDBPs) (e.g. Rs12565727), autism susceptibility gene 2 (AUTS2) (e.g., Rs 6945541), SET binding protein 1 (SETBP1) (e.g., Rs105 02861), 17q21.31 (e.g., Rs12373124), tumor necrosis Factor receptor superfamily member 6B (TNFRSF6B) (e.g., Rs601 0620, etc.), zinc finger CCCH with G patch domain-containing proteins type (ZGPAT) (e.g., Rs6010620, etc.), P2X purinergic receptor 7 (P 2RX7) (e.g. Rs17525809, Rs28360447, Rs795831 1, Rs1718119, Rs2230912, Rs28360457, Rs22309 11, and / or Rs1653624), oxytocin receptors (e.g., Rs2 37887, Rs2268491, Rs2254298, and / or Rs76322 87), non-coding RNA (ncRNA) (e.g., Rs11669309, Rs22 98075, and / or Rs10237038), long non-coding RNA (lnc RNA) (e.g. Rs8028149, Rs16868911, Rs11543230 , Rs9309325, Rs12951337, Rs15428265, Rs12683 158, and / or Rs6982502), human leukocyte antigens (HLA) (e.g. , Rs2269706, etc.), platelet-derived growth factor (PDGF) receptor (PDGFR) B (PDGFR-B), tissue inhibitor of metalloproteinases (TIMP) 1 (TIMP-1) , TIMP-2, IL-23, activin A, intercellular adhesion molecule (ICAM-2), osteoclasts Opontin (OPN), insulin, insulin growth factor binding protein 4 (IGF-B P4), tumor necrosis factor (TNF) receptor 1 (TNF-R1), ectodysplasin A2 receptor The gene is present in one or more genes encoding the receptor (XEDAR), and / or follistatin. It contains one or more SNPs present in

[0008] In one aspect, the use in treating a disease or disorder in an end-user subject. Disclosed herein is a mesenchymal stem cell and exosome therapeutic composition for a) a composition base; and b) a composition having the same hair type, hair color, skin type, and skin color as the end user. , race, and / or ethnicity, but the donor is never Single nucleotide polymorphism (SNP) profiles that indicate the absence of a disease or disorder and a mesenchymal stem cell and exosome preparation derived from a donor having MS. C and exosome preparations were performed using cells or cell cultures cultured under normal hyperoxic culture conditions. and cells cultured under harsh wound healing conditions. Each contains one member.

[0009] Also disclosed herein are mesenchymal stem cell and exosome therapeutic compositions of any of the preceding aspects. , SNPs include interleukin 18 (IL-18) (e.g., rs1946518 and / or rs187238, etc.), androgen receptor (AR) (e.g., Rs6152 , Rs2223841, and / or Rs2497938), histone deacetylase (HDAC)-4 (HDAC4) (e.g., Rs9287638), HDAC9 (e.g. For example, Rs2073963 and / or Rs2180439), paired boxes 1(PAX1) (e.g., Rs1160312 and / or Rs6047844) , Forkhead box A2 (FOXA2) (e.g., Rs1160312 and / or or Rs6047844), TAR DNA-binding proteins (TARDBPs) (e.g. Rs12565727), autism susceptibility gene 2 (AUTS2) (e.g., Rs 6945541), SET binding protein 1 (SETBP1) (e.g., Rs105 02861), 17q21.31 (e.g., Rs12373124), tumor necrosis Factor receptor superfamily member 6B (TNFRSF6B) (e.g., Rs601 0620, etc.), zinc finger CCCH with G patch domain-containing proteins type (ZGPAT) (e.g., Rs6010620, etc.), P2X purinergic receptor 7 (P 2RX7) (e.g. Rs17525809, Rs28360447, Rs795831 1, Rs1718119, Rs2230912, Rs28360457, Rs22309 11, and / or Rs1653624), oxytocin receptors (e.g., Rs2 37887, Rs2268491, Rs2254298, and / or Rs76322 87), non-coding RNA (ncRNA) (e.g., Rs11669309, Rs22 98075, and / or Rs10237038), long non-coding RNA (lnc RNA) (e.g. Rs8028149, Rs16868911, Rs11543230 , Rs9309325, Rs12951337, Rs15428265, Rs12683 158, and / or Rs6982502), human leukocyte antigens (HLA) (e.g. , Rs2269706, etc.), platelet-derived growth factor (PDGF) receptor (PDGFR) B (PDGFR-B), tissue inhibitor of metalloproteinases (TIMP) 1 (TIMP-1) , TIMP-2, IL-23, activin A, intercellular adhesion molecule (ICAM-2), osteoclasts Opontin (OPN), insulin, insulin growth factor binding protein 4 (IGF-B P4), tumor necrosis factor (TNF) receptor 1 (TNF-R1), ectodysplasin A2 receptor The gene is present in one or more genes encoding the receptor (XEDAR), and / or follistatin. It contains one or more SNPs present in

[0010] In one aspect, the mesenchymal stem cell and exosome therapeutic composition of any preceding aspect The method of treating a disease or disorder in a subject, including administering to the subject Atopic dermatitis, autism spectrum disorder, multiple sclerosis, chronic pain, depression, anxiety, Bipolar disorder, osteoporosis, rheumatoid arthritis, celiac disease, type II diabetes, coronary heart disease, The present invention relates to the treatment, inhibition, reduction, amelioration, prevention, and / or administration of any of the following drugs: Methods for inhibiting and / or reversing the process are disclosed herein.

[0011] For example, in one embodiment, a method for treating, inhibiting, reducing, ameliorating, inhibiting ... Disclosed herein are methods for preventing and / or reversing the disease or disorder, wherein the disease or disorder is alopecia (e.g., For example, male pattern baldness, androgenetic alopecia, alopecia areata, cicatricial alopecia, telogen effluvium, or female pattern hair loss), and a single nucleotide polymorphism associated with alopecia in the subject (SNP) is SNP Rs6152, Rs2223841, Rs2497938, Rs 1160312, 6047844, Rs2180439, Rs2073963, Rs12 565727, Rs9287638, Rs6945541, Rs12373124, Rs 10502861, Rs187238, and / or Rs1946518 Including the above.

[0012] Treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Also disclosed herein are methods of reversing, wherein the cancer comprises pancreatic cancer or breast cancer. The present invention relates to a method for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder of the preceding aspect of the present invention. Disclosed herein is a method for detecting a SNP associated with breast cancer in a subject, the method comprising: The present invention relates to a method for treating, inhibiting, or preventing a disease or disorder of any of the preceding aspects. Also disclosed herein are methods of reducing, ameliorating, preventing, and / or reversing the disease, wherein the disease is pancreatic cancer. and SNPs associated with pancreatic cancer in subjects include SNP Rs10237038.

[0013] In one aspect, the present invention relates to a method for treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Disclosed herein are methods for preventing and / or reversing the disease or disorder, wherein the disease or disorder is autism spectrum disorder. The SNPs associated with autism spectrum disorder include SNP Rs237887, Of Rs2,268,491, Rs2,254,298, and / or Rs7,632,287 Contains one or more.

[0014] Treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Also disclosed herein are methods of reversing, wherein the disease or disorder comprises osteoporosis, The associated SNPs are SNPs Rs28360447, Rs28360457, and Rs1718 119, Rs2230911, and / or Rs1653624 nothing.

[0015] In one aspect, the present invention relates to a method for treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Disclosed herein are methods for causing and / or reversing the disease or disorder, wherein the disease or disorder includes rheumatoid arthritis. , SNPs associated with rheumatoid arthritis include SNP Rs2269706.

[0016] Treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Also disclosed herein are methods of reversing, wherein the disease or disorder comprises multiple sclerosis, The SNPs associated with the disease are SNPs Rs17525809 and / or Rs2836044 Contains one or more of 7.

[0017] In one aspect, the present invention relates to a method for treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Disclosed herein are methods for causing and / or reversing chronic pain, wherein the disease or disorder includes chronic pain, The SNPs associated with sexual pain were SNPs Rs28360447 and / or Rs79583 Contains one or more of 11.

[0018] Treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Also disclosed herein are methods of reversing, wherein the disease or disorder comprises atopic dermatitis, SNPs associated with idiopathic dermatitis include SNP Rs6010620.

[0019] In one aspect, the present invention relates to a method for treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Disclosed herein are methods for causing and / or reversing hypertension, SNPs associated with pressure include SNP Rs11669309.

[0020] Treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Also disclosed herein are methods of reversing, wherein the disease or disorder comprises coronary heart disease, Associated SNPs include SNP Rs6982502.

[0021] In one aspect, the present invention relates to a method for treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Disclosed herein are methods for preventing and / or reversing the disease or disorder, wherein the disease or disorder includes type II diabetes. , SNPs associated with type II diabetes include SNP Rs12683158.

[0022] Treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Also disclosed herein are methods of reversing the disease or disorder, wherein the disease or disorder comprises celiac disease, Disease-associated SNPs include SNP Rs15428265.

[0023] In one aspect, the present invention relates to a method for treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Disclosed herein are methods for treating and / or reversing the disease or disorder anxiety, and anxiety-related The SNPs involved include SNP Rs1718119.

[0024] Treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Also disclosed herein are methods of reversing, wherein the disease or disorder comprises bipolar disorder, Associated SNPs include SNP Rs2230912.

[0025] In one aspect, the present invention relates to a method for treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Disclosed herein are methods for causing and / or reversing a disease or disorder, the disease or disorder including depression, Disease-associated SNPs include SNP Rs8028149.

[0026] Treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Also disclosed herein is a method of reversing a disease or disorder comprising identifying an individual with SNP Rs16868911 , Rs11,543,230, Rs9,309,325, and / or Rs12,951,337 Contains one or more of the following: DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] Before the compounds, compositions, articles, devices, and / or methods are disclosed and described , which may of course vary, unless otherwise specified, a particular synthesis method or a particular It is not limited to recombinant biotechnology methods and, unless otherwise specified, is not limited to specific reagents. It should be understood that the terminology used herein is intended to describe particular embodiments. It should also be understood that these are for illustrative purposes only and are not intended to be limiting.

[0028] A.Definition As used in this specification and the appended claims, the singular forms "a," "an," " " and "the" include plural referents unless the context clearly indicates otherwise. For example, reference to "a pharmaceutical carrier" includes mixtures of two or more such carriers, and the like.

[0029] Ranges are expressed herein as from "about" one particular value, and / or to "about" another particular value. When such a range is expressed, another embodiment may include any one particular value. and / or to another specified value. Similarly, when values ​​are expressed as approximations, It is understood that by use of the antecedent "about," the particular value forms another embodiment. Each endpoint of the range will be relevant in relation to and in relation to the other endpoints. It will be further understood that both are important, independent of the endpoint. It is understood that there are several values ​​disclosed in the specification, and that each value is also expressly stated as "about" in addition to the value itself. It is also understood that specific values ​​are disclosed herein. For example, the value "10 " is disclosed, "about 10" is also disclosed. If a value is disclosed as "less than or equal to" that value, "greater than or equal to" and any possible range between the values It is also understood that ranges are disclosed. For example, if the value "10" is disclosed, the disclosure includes "less than or equal to 10". " as well as "10 or more." Throughout this application, data is presented in several different forms. The data will be provided in the formula and will include endpoints and starting points, etc. It is also understood that any combination of the data points represents a range. For example, if a specific data point “10” and a specific data point “15” are disclosed, Overall, more than 10 and more than 15, 10 or more and 15 or more, less than 10 and less than 15, 10 or less and 15 and below, as well as 10 and 15, are considered to be disclosed in the same manner as 10-15. It is understood that each unit between two particular units is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0030] The term "subject" refers to any animal, including primates (e.g., humans), cows, horses, pigs, sheep, goats, dogs, Animals, such as mammals, including but not limited to cats, rabbits, rats, mice, etc. In some embodiments, the subject is a human.

[0031] "Administration" to a subject includes any route of introducing or delivering an agent to a subject. Oral, topical, intravenous, subcutaneous, transcutaneous, transdermal ermal), intramuscular, intraarticular, parenteral, intraarterial, intradermal, intraventricular, intracranial, intraperitoneal, focal intravenously, intranasally, rectally, intravaginally, by inhalation, via an implanted reservoir, parenterally (e.g. Subcutaneous, intravenous, intramuscular, intraarticular, intrasynovial, intrasternal, intrathecal, intraperitoneal, intrahepatic, intralesional, The technique may be performed by any suitable route, including intracranial and intracranial injection or infusion techniques. As used herein, "concurrent administration" and "co-administration" are used interchangeably. "simultaneous administration" or "administered at the same time" refers to are administered at the same time or essentially immediately after each other. The two compounds were administered at the same time to ensure that the observed results were achieved when the compounds were administered at the same time. "Systemic administration" refers to administration that is administered to the circulatory or respiratory system in a manner sufficiently close in time to be indistinguishable from the The drug is delivered to a large area of ​​the target body (e.g., more than 50% of the body) through an entrance into the immune system. Refers to the introduction or delivery of a drug to a subject through a route of introduction or delivery. "Local administration" refers to the introduction or delivery of an agent to an area or areas immediately adjacent to the point of administration; Introducing or delivering an agent to a subject via a route that does not introduce the agent systemically in therapeutically significant amounts For example, a locally administered drug should be readily detectable in the local vicinity of the point of administration. but is undetectable or detectable in negligible amounts in distal parts of the subject's body Administration includes self-administration and the administration by another.

[0032] "Biocompatible" refers to a compound that is generally non-toxic to the recipient and does not cause significant adverse effects in the subject. "Non-toxic" refers to a material and any of its metabolic or decomposition products that do not cause side effects such as toxicological or toxicological effects.

[0033] "Comprising" means that the composition, method, etc. includes the recited elements but does not exclude others. " when used to define compositions and methods. "Consisting essentially of" includes the recited elements but does not include any essential weight for the combination. It is intended to mean excluding other elements of the requirement as defined herein. A composition consisting essentially of such elements is free of trace contaminants, if any, from the isolation and purification process. and phosphate buffered saline, preservatives, and the like. "Consists of" means that the composition is made up of trace elements of other ingredients and a substantial method for administering the composition of the present invention. Each of these transitional terms means to exclude one or more method steps. Embodiments defined accordingly are within the scope of the present invention.

[0034] A "control" is an alternative subject or sample used in an experiment for comparative purposes. Controls can be "positive" or "negative."

[0035] "Controlled release" or "sustained release" refers to a compound that achieves a desired pharmacokinetic profile in vivo. "Controlled release" refers to the release of a drug from a given dosage form in a controlled manner in order to deliver the drug. In one embodiment, the formulation and / or dosage form is manipulated to establish desired kinetics of drug release. It is the ability to do so.

[0036] An "effective amount" of a drug refers to a sufficient amount of the drug to provide a desired effect. The amount of drug administered depends on many factors, including the age and general condition of the subject and the specific drug(s). Therefore, it is not possible to specify a quantified "effective amount." However, it is possible to determine an appropriate "effective amount" in any given subject case. can be determined by one of ordinary skill in the art using routine experimentation. In certain instances, unless otherwise specified, an "effective amount" of an agent includes both a therapeutically effective amount and a prophylactically effective amount. An "effective amount" of a drug required to achieve a therapeutic effect can also refer to an amount that encompasses the amount of the drug that is administered to the subject. The dosage regimen may vary according to factors such as age, sex, and weight. For example, several divided doses can be administered daily, Alternatively, the dosage may be proportionally reduced as indicated by the exigencies of the therapeutic situation.

[0037] "Reduction" refers to a smaller amount of gene expression, protein production, symptom, disease, composition, condition, A substance can also refer to any change that results in a gene having a substance. When the genetic output of the offspring is less than the output of the gene product without the substance, the genetic This is understood to mean reducing the genetic output of the offspring. Also, for example, the reduction may be due to the condition being more severe than previously observed. The reduction may be a change in the symptoms of a disorder that is less than expected. The reduction may be any individual, median, or average reduction in a condition, symptom, activity, or composition. Therefore, a decrease is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 , 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, It may be a 75, 80, 85, 90, 95, or 100% reduction.

[0038] "Inhibit," "inhibiting," and "inhibition" refer to an activity, response, condition, disease, or This means that the activity, response, and state of the body are decreased. This can include, but is not limited to, complete disappearance of the disease. Also, for example, a decrease in the activity, response, condition, or disease, as compared to native or control levels. A reduction may also include a 10% reduction. Thus, a reduction is a reduction in a level relative to a native or control level. , 10, 20, 30, 40, 50, 60, 70, 80, 90, 100% or any of these The reduction may be any amount between.

[0039] The terms "prevent", "preventing", "prevention" and grammatical variations thereof are used herein. As used herein, the occurrence of a disease and / or one or more of its associated symptoms. or partially or completely delay or eliminate recurrence or prevent the subject from acquiring the disease. or prevents the subject from regaining the ability to express or express the disease or its associated symptoms. The term refers to a method of reducing the risk of acquiring or losing one or more of the following:

[0040] A "pharmacologically acceptable" component is a component that is not biologically or otherwise undesirable. component, i.e., without causing or resulting in significant undesirable biological effects without interacting in a deleterious manner with any of the other components of the formulation in which it is included, As described herein, it can be incorporated into a pharmaceutical formulation of the invention and administered to a subject. When used in reference to administration to humans, the term generally refers to The components have met the required standards of toxicity and manufacturing testing, or Inactive Ingredient Guidance prepared by the U.S. Food and Drug Administration It means it is included in the ide.

[0041] A "pharmaceutically acceptable carrier" (sometimes referred to as a "carrier") is generally a safe and means a carrier or excipient that is useful in preparing a pharmaceutical or therapeutic composition that is toxic. , including carriers acceptable for veterinary and / or human pharmaceutical or therapeutic use. "Carrier" or "Pharmaceutically acceptable carrier" refers to any suitable carrier, including, but not limited to, phosphate buffered saline solution, water, emulsions, etc. emulsions (e.g., oil / water or water / oil emulsions) and / or various types of wetting As used herein, the term "carrier" can include, but is not limited to, "Form" refers to any excipient for use in a pharmaceutical formulation and as further described herein. agents, diluents, bulking agents, salts, buffers, stabilizers, solubilizers, lipids, stabilizers, or compounds of the art These include, but are not limited to, other materials well known in the art.

[0042] "Pharmacological activity" (or simply "activity") refers to a "pharmacologically active" derivative or analogue. In the case of a compound with a similar type of pharmacological activity to the parent compound, the compound induces approximately the same degree of activity. or analogs (e.g., salts, esters, amides, conjugates, metabolites, isomers, It can refer to a fragment, etc.

[0043] "Therapeutic agent" refers to any composition that has a beneficial biological effect. The compounds may have therapeutic effects, e.g., treatment of a disorder or other undesirable physiological condition, and preventive effects. The effect is, for example, prevention of a disorder or other undesirable physiological condition (e.g., non-immunogenic cancer). The term also includes salts, esters, amides, proagents, active metabolites, Any isomers, fragments, analogs, etc. specifically mentioned herein include, but are not limited to, isomers, fragments, analogs, etc. The term "therapeutic agent" includes pharma- ceutically acceptable and pharmacologically active derivatives of the beneficial agent. When "therapeutic agent" is used or when a particular agent is specifically identified, the term refers to the agent itself. The compounds of the present invention include, as well as pharma- ceutically acceptable and pharmacologically active salts, esters, amides, proagents, and the like. , conjugates, active metabolites, isomers, fragments, analogs, and the like. stomach.

[0044] "Polymer" refers to a natural or synthetic organic compound of relatively high molecular weight, the structure of which is A polymer may be represented by a monomer, which is a repeating small unit. A non-limiting example of a polymer is a polymer. Synthetic polymers are typically produced by the addition or synthesis of monomers. The term "copolymer" refers to a polymer formed by polymerization of two or more different repeating units. A polymer formed from units (monomer residues) is an example, but is not limited to, a copolymer. The copolymer may be an alternating copolymer, a random copolymer, a block copolymer, or a graft copolymer. In certain embodiments, the various block segments of a block copolymer may be It is also contemplated that the component itself may comprise a copolymer. Natural polymers, synthetic polymers, homopolymers, heteropolymers or copolymers, addition polymers The term includes all forms of polymers, including, but not limited to, mers, etc.

[0045] A "therapeutically effective amount" or "therapeutically effective dose" of a composition (e.g., a composition that includes a drug) is In some embodiments, the desired therapeutic result is achieved by administering to the subject a therapeutically effective amount. The outcome is control of type I diabetes. In some embodiments, the desired therapeutic outcome is reduction of obesity. The therapeutically effective amount of a given therapeutic agent is typically determined based on the type of disorder or disease being treated. The type and severity of the disease may vary, as well as factors such as the age, sex, and weight of the subject. The term also refers to a compound that is effective in promoting a desired therapeutic effect, such as pain (i.e., pain sensation) relief. It can refer to the amount of therapeutic agent effective, or the delivery rate of the therapeutic agent (e.g., amount over time). The precise desired therapeutic effect will depend on the condition being treated, the tolerance of the subject, the agent being administered and / or or drug formulation (e.g., potency of therapeutic agent, concentration of agent in the formulation, etc.), as well as other properties that will be readily understood by those of skill in the art. In some cases, the desired biological The therapeutic or medical response may be a response to a composition administered to a subject over a period of days, weeks, or years. This is achieved after administration of multiple doses of

[0046] As used herein and in the claims that follow, references are defined to have the following meanings: This will be done for some terms that are to be considered.

[0047] "Optional" or "optionally" means that the following events or circumstances occur: The events or circumstances described may or may not occur and may not be instances in which such events or circumstances may occur or This means that it includes cases where the condition does not occur.

[0048] Throughout this application, various publications are referenced. No. 6,399,945, filed on Oct. 13, 2003. The disclosures herein are hereby incorporated by reference in their entirety in order to more fully describe the state of the art to which this relates. The references disclosed are also discussed in the text in which they are relied upon. The material contained in each such publication is individually and specifically incorporated by reference herein. can be.

[0049] B. Composition The components used to prepare the disclosed compositions, as well as the The compositions themselves used in the methods are disclosed. These and other materials are disclosed herein. As set forth herein, and as combinations, subsets, interactions, groups, etc. of these materials are disclosed, Specific examples of various individual and collective combinations and permutations of each of these compounds are given below. While the references may not be explicitly disclosed, each is specifically contemplated and described herein. For example, it is understood that certain therapeutic compositions (growth factors, exosomes, etc.) may be used. or compositions comprising proteins derived from MSCs are disclosed and contemplated, (e.g., compositions containing growth factors, exosomes, or proteins derived from MSCs) In particular, when considering several modifications that can be made to several molecules, including Therapeutic compositions (such as compositions containing growth factors, exosomes, or proteins derived from MSCs) etc.) and each and every combination and modification possible unless specifically indicated to the contrary. Thus, classes of molecules A, B, and C, Similarly, when classes of molecules D, E, and F, as well as examples of combination molecules, are disclosed, -D is disclosed and then each is individually and Collectively contemplated, combinations include AE, AF, BD, BE, BF, CD, C -E, and CF are considered to be disclosed. Similarly, any of these Any subset or combination is also disclosed. Thus, for example, AE, BF, and and the subgroups of CE would be considered disclosed. The present invention includes, but is not limited to, steps in methods of making and using the compositions. This applies to all aspects of the present application. Thus, there may be various additional steps that may be performed. In this case, each of these additional steps is not essential to any particular embodiment or implementation of the disclosed methods. It will be appreciated that a combination of embodiments may be used.

[0050] Individual genotype influences the expression of and response to exosomes and growth factors This recognition has been confirmed by recombinant proteins or platelet-rich Individualized use of responsive drugs rather than doses of autologous growth factors such as plasma (PRP) It provides confidence in the philosophy of chemical medicine. The growth conditions in the laboratory are It is well known that the amount of MSCs in the culture medium can be significantly affected. Exposure to low conditions dramatically increased the amount of released growth factors and exosomes. Studies have shown that the effect of regulating the proliferation of endothelial cells is not conclusive. Proteome of MSC growth factors and MSC-derived exosomes from cells cultured under to assess important angiogenesis factors that are present under these conditions and potentially differentially expressed. In total, 6,342 proteins were identified as MSC growth factors. 1,927 proteins were identified in the IL-16 protein-binding domain from cells subjected to stressful growth conditions. The results showed that exosomes derived from MSCs are more efficient at inhibiting oxidative stress compared to those grown under ideal conditions. Different patterns of growth factors and exosomes produced by cells grown under stress conditions There has been a substantial increase in the quantity and number of types.

[0051] Multi-layer analysis revealed that expression was upregulated in MSCs exposed to simulated stress ischemic conditions. We identified several growth factors and exosomes that stimulated significantly increased angiogenesis. These growth factor proteins include platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor. , and most notably, nuclear factor-kappa B (NFkB) signaling pathway proteins. Collectively, the results of proteomic analyses from previous studies have demonstrated that MSC-derived growth factors and endogenous Xosomes are potent antagonists of angiogenic paracrine effectors with therapeutic potential for multiple diseases. indicates that the sample contains a healthy profile.

[0052] In one embodiment, the present invention provides a method for treating, inhibiting, reducing, alopecia, gray hair, erectile dysfunction, and / or skin disorders. A physical characteristic of a subject (e.g., skin color, skin type, ethnicity, race, hair type, and / or hair color) specific therapeutic compositions are described herein. As disclosed herein, the therapeutic composition comprises MSCs or similar fibroblasts. Concentrated growth factors derived from exon-like cells, keratinocytes or melanocytes Some, extracellular proteins, proteoglycans, cytokines, chemokines, proteins and peptides, and the cells may be cultured in bone marrow, adipose (adipocytes) or other tissues prior to or after cell expansion. ipose (fat), stromal vascular fraction (SVF), bone, or other tissue sources. In some embodiments, the therapeutic composition further comprises stem cell factor (SCF). It is possible.

[0053] Exosomes are small (30-200 nm) membrane-bound vesicles that are released into the extracellular environment. Exosomes contain growth factors, signaling lipids, and messenger RNA (mRNA). It contains various types of RNA that induce RNA (RNA) and microRNA (miRNA). Their RNA content accounts for most of the cellular effects that exosomes deliver. In the absence of this, RNA is transported by the Golgi apparatus in donor MSCs to numerous peptides. These are placed into exosomes along with tRNA, growth factors, and signaling lipids. The exact types and amounts of growth factor proteins, signaling lipids, and RNA that are placed within The amount and concentration of MSCs depends on the surrounding microenvironment and the signals to which the MSCs are exposed.

[0054] Thus, the disease or disorder in a subject (e.g., alopecia, atopic dermatitis, autism, dementia spectrum disorder, multiple sclerosis, chronic pain, depression, anxiety, bipolar disorder, osteoporosis, Rheumatoid arthritis, celiac disease, type II diabetes, coronary heart disease, hypertension, multiple complex diseases to treat, inhibit, reduce, ameliorate, prevent, and / or reverse a disease, such as a cancer, Disclosed herein are methods for producing mesenchymal stem cell and exosome therapeutic compositions for The method includes: a) identifying the end user's hair, skin color, skin type, race, or ethnicity; and b) determining whether a single nucleotide polymorphism (SNP) is associated with a disease or disorder in the subject. and c) to identify individuals with the same hair type, color, and / or ethnicity as the subject, but without Single nucleotide polymorphism (SNP) profiles that indicate that a patient will never experience a disease or disorder obtaining mesenchymal stem cells (MSCs) from a targeted donor having a specific profile; and d) and preparing an MSC and exosome preparation from the obtained MSCs. and the exosome preparation comprises and / or contains a corrective SNP and a cytokine. MSCs secreting exosomes were generated in a medium containing sufficient growth conditions to generate MSCs and exosomes that secrete MSCs. They are generated by culturing SCs.

[0055] In some embodiments, the method includes tacking growth factors in MSC and exosome preparations. The analysis of the growth factor and exosome preparations further includes identifying the type and amount of the may involve any means known in the art for analyzing proteins and nucleic acids. It is understood that growth factors are primarily proteins and peptides. Growth factors can be identified by mass spectrometry, protein arrays, protein chips, enzyme-linked immunosorbent assays, and Assay (ELISA), flow cytometry, enzyme-linked immunospot (ELISpo t), SDS-PAGE, mass spectrometry immunoassay (MSIA), electrospray ionization ionization, matrix-assisted laser desorption / ionization (MALDI), Western blot, and / or chromatography, known in the art, The proteins may be analyzed using any of the methods of proteomic analysis described above. In addition to exosome cargo, exosomes can also carry RNA that has profound effects on target cells. The proteomic cargo of exosomes is similar to that used to detect growth factors. Nucleic acids contained in exosomes can be detected using the same techniques. Detection and characterization of nucleic acids, including but not limited to arrays, PCR, and Northern blots The proteins may be characterized by any technique useful in identification and characterization.

[0056] Some embodiments of the present disclosure provide a method for treating a particular medical condition, unique facial problem, race, or ethnicity. The present invention also includes a method for producing a mesenchymal stem cell and exosome therapeutic composition comprising: Identify single nucleotide polymorphisms (SNPs) of potential donors to match those of end users Matching and donors with the same or similar SNP profile as the end user and obtaining mesenchymal skin cells (MSCs) from the obtained MSCs, and and preparing an exosome preparation. The MSC preparation may comprise: Maximize treatment effectiveness by matching the exact condition that needs to be treated and treated To investigate the mechanism of action of growth factors in the proliferation of IL-1, a thorough characterization and proteomic analysis of the growth factors and the proliferation medium were performed. Molecular characterization of the exosomal RNA present can be used to match specific disease states in recipients. These can be engineered by modifying growth conditions to produce specific products.

[0057] As discussed above, the disclosed methods include the detection and use of SNPs associated with disease states, and have similar racial, hair, eye, skin, and / or ethnic characteristics as the recipient, but and SNPs relating to the disclosed methods of making mesenchymal stem cell and exosome therapeutic compositions. It is understood and contemplated herein that the amount of blood used may vary depending on the donor used. The SNPs identified may be associated with a disease or disorder that is being targeted for treatment, as well as with the endogenous It is understood that the results are dependent on the user's subject (which must differ in SNPs from the donor). Thus, in one aspect of the present invention, a method is provided for detecting a disease in a subject. Diseases or disorders (e.g., alopecia, atopic dermatitis, autism spectrum disorder, multiple sclerosis) chronic pain, depression, anxiety, bipolar disorder, osteoporosis, rheumatoid arthritis, celiac disease, type II diabetes, coronary heart disease, hypertension, multiple coexisting diseases, and / or cancer MESH CELLS AND EXO-STEM CELLS FOR TREATING, INHIBITING, REDUCING, AMELIORATING, PREVENTING, AND / OR REVERSING The present invention is directed to preparing a method for the treatment of a disease or disorder, the disease or disorder being alopecia (e.g., male pattern baldness). Male pattern alopecia, androgenetic alopecia, alopecia areata, cicatricial alopecia, telogen effluvium, or female pattern alopecia androgenetic alopecia, etc.), and a single nucleotide polymorphism (SNP) associated with alopecia in a subject. ) is SNP Rs6152, Rs2223841, Rs2497938, Rs1160 312, 6047844, Rs2180439, Rs2073963, Rs125657 27, Rs9287638, Rs6945541, Rs12373124, Rs1050 2861, Rs187238, and / or Rs1946518 Similarly, in one aspect, a method for treating, inhibiting, reducing, ameliorating, preventing, or inhibiting autism spectrum disorders is provided. To create mesenchymal stem cell and exosome therapeutic compositions for the treatment and / or reversal of Disclosed herein is a method for determining whether a SNP associated with autism spectrum disorder is SNP R s237887, Rs2268491, Rs2254298, and / or Rs763 2287. or methods for preparing mesenchymal stem cell and exosome therapeutic compositions for reversing the effects of the present invention Also disclosed herein are SNPs associated with osteoporosis, including SNP Rs28360447, Rs28360457, Rs1718119, Rs2230911, and / or Rs 1653624. In one embodiment, the method comprises treating, inhibiting, or reducing rheumatoid arthritis. US20130233633A1 - Mesenchymal stem cell and exosome therapeutic compositions for improving, preventing, and / or reversing ... - Google Patents Disclosed herein are methods for making the products, and the SNPs associated with rheumatoid arthritis are P Rs2269706. Treat, inhibit, reduce, ameliorate, prevent, and and / or a method for creating a mesenchymal stem cell and exosome therapeutic composition for reversing Also disclosed herein is a method for determining whether a SNP associated with multiple sclerosis is SNP Rs175258 In one embodiment, the method comprises administering to the subject one or more of the following: Mesenchymal stem cells and Disclosed herein are methods for making exosome therapeutic compositions, and for treating chronic pain-related conditions. The SNPs involved are SNPs Rs28360447 and / or Rs7958311. The present invention relates to a method for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing atopic dermatitis. Methods for producing mesenchymal stem cell and exosome therapeutic compositions for transfection are also described herein. and comprising SNP Rs6010620. In one embodiment, the method is for treating, inhibiting, or preventing hypertension. Mesenchymal stem cell and exosome therapy to reduce, ameliorate, prevent, and / or reverse Methods for making compositions are disclosed herein, and the SNP associated with hypertension is SNP Contains Rs11669309. For treating, inhibiting, reducing, ameliorating, preventing, and To create a mesenchymal stem cell and exosome therapeutic composition for preventing and / or reversing A method is also disclosed herein, wherein the SNP associated with coronary heart disease is SNP Rs6982 In one embodiment, the method includes the steps of treating, inhibiting, reducing, ameliorating, preventing, and / or treating type II diabetes. and methods for preparing mesenchymal stem cell and exosome therapeutic compositions for reversing or reversing SNPs disclosed herein that are associated with type II diabetes include Rs12683158. Mesenchymal stem cells for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing celiac disease Methods for making cell and exosome therapeutic compositions are also disclosed herein, including the use of ceria. SNPs associated with Crohn's disease include SNP Rs15428265. Mesenchymal stem cells and exogenous ... Disclosed herein are methods for making sosomal therapeutic compositions, comprising a SNP associated with anxiety. contains SNP Rs1718119. and / or to create a mesenchymal stem cell and exosome therapeutic composition for reversing Also disclosed herein is a method for detecting a SNP associated with bipolar disorder, the SNP being SNP Rs2230 In one embodiment, the method includes treating, inhibiting, reducing, ameliorating, preventing, and / or reversing depression. Methods for producing mesenchymal stem cell and exosome therapeutic compositions for translocation are described herein. SNPs disclosed in the literature and associated with depression include SNP Rs8028149. US20130236333A1 - Mesenchymal stem cells for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder - Google Patents Also disclosed herein are methods for producing exosome therapeutic compositions, Disability, SNP Rs16868911, Rs11543230, Rs9309325, and / or one or more of Rs12,951,337.

[0058] In one aspect, the disclosed method for producing a mesenchymal stem cell and exosome therapeutic composition is The method includes administering to a subject a therapeutic biomarker for treating any disease in which uncontrolled cell proliferation occurs, such as cancer. It is understood that the present invention can be used for the MSC and exosome compositions produced by the present invention. Representative of the cancers that the disclosed compositions can be used to treat are: A non-limiting list is: lymphoma, B-cell lymphoma, T-cell lymphoma, mycosis Sarcoidosis, Hodgkin's disease, myeloid leukemia, bladder cancer, brain cancer, nervous system cancer, head and neck cancer, squamous cell carcinoma of the head and neck Lung cancer, including epithelial cell carcinoma, small cell lung cancer and non-small cell lung cancer; Glioblastoma / metastasis, ovarian cancer, skin cancer, liver cancer, melanoma, oral cavity, throat, larynx, and lung squamous cell carcinoma Epithelial cell carcinoma, cervical cancer, cervical carcinoma, breast cancer, as well as epithelial cancer, renal cancer, urogenital cancer Cancer, lung cancer (pulmonary cancer), esophageal carcinoma, head and neck carcinoma, colorectal cancer, hematopoiesis In one embodiment, the cancer is a cancer of the rectum, prostate, or pancreas. Mesenchymal stem cells and enzymes for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing Disclosed herein are methods for making xosome therapeutic compositions, the cancer being pancreatic cancer or breast cancer. In one embodiment, to treat, inhibit, reduce, ameliorate, prevent, and / or reverse breast cancer. Disclosed herein are methods for producing mesenchymal stem cell and exosome therapeutic compositions, SNPs associated with breast cancer in elephants include SNP Rs2298075. Treat pancreatic cancer Mesenchymal stem cells and exosomal cells for inhibiting, reducing, ameliorating, preventing, and / or reversing Also disclosed herein are methods of making a pancreatic cancer therapeutic composition, comprising administering to a subject a pancreatic cancer-associated S. NPs include SNP Rs10237038.

[0059] It is understood that the disclosed SNPs are associated with point mutations in the nucleic acid of a particular gene; Contemplated herein. Thus, in one aspect, a disease or disorder (e.g., , alopecia, atopic dermatitis, autism spectrum disorder, multiple sclerosis, chronic pain, depression Disease, anxiety, bipolar disorder, osteoporosis, rheumatoid arthritis, celiac disease, type II diabetes, coronary artery Treating, inhibiting, reducing, or ameliorating chronic heart disease, hypertension, multiple coexisting diseases, and / or cancer The present invention provides a method for producing mesenchymal stem cell and exosome therapeutic compositions for preventing, preventing, and / or reversing The present invention relates to a method for producing a gene encoding an interleukin 18 (IL-18) gene, comprising: , rs1946518 and / or rs187238), androgen receptor (A R) (e.g., Rs6152, Rs2223841, and / or Rs2497938 ), histone deacetylase (HDAC)-4 (HDAC4) (e.g., Rs92876 38), HDAC9 (e.g., Rs2073963 and / or Rs218043 9), paired box 1 (PAX1) (e.g., Rs1160312 and / or Forkhead Box A2 (FOXA2) (e.g., Rs6047844) s1160312 and / or Rs6047844), TAR DNA binding protein TARDBP (e.g., Rs12565727), autism susceptibility gene 2 ( AUTS2) (e.g., Rs6945541), SET-binding protein 1 (SETB P1) (e.g., Rs10502861, etc.), 17q21.31 (e.g., Rs123 73124, etc.), tumor necrosis factor receptor superfamily member 6B (TNFRSF 6B) (e.g., Rs6010620, etc.), which has a G-patch domain-containing protein Zinc finger CCCH type (ZGPAT) (e.g., Rs6010620, etc.) , P2X purinergic receptor 7 (P2RX7) (e.g., Rs17525809, Rs2836 0447, Rs7958311, Rs1718119, Rs2230912, Rs283 60457, Rs2230911, and / or Rs1653624, etc.), Oxyto Synth receptors (e.g., Rs237887, Rs2268491, Rs2254298, and and / or Rs7632287), non-coding RNA (ncRNA) (e.g., Rs 11669309, Rs2298075, and / or Rs10237038 etc.), Long non-coding RNAs (lncRNAs) (e.g., Rs8028149, Rs168689 11, Rs11543230, Rs9309325, Rs12951337, Rs154 28265, Rs12683158, and / or Rs6982502, etc.), human white blood cells Human leukocyte antigens (HLA) (e.g., Rs2269706, etc.), platelet-derived growth factor (PDG F) Receptor (PDGFR) B (PDGFR-B), tissue inhibitor of metalloproteinase (T TIMP-1 (TIMP-1), TIMP-2, IL-23, activin A, cell-cell adhesion molecule ICAM-2, osteopontin (OPN), insulin, insulin growth factor binding Integrative Growth Factor-BP4 (IGF-BP4), Tumor Necrosis Factor (TNF) Receptor 1 (TNF-R1) , ectodysplasia receptor A2 (XEDAR), and / or follistatin. The gene expression vector contains one or more SNPs present in one or more genes that are involved in the analysis.

[0060] The disclosed methods include administering to a subject a therapeutically effective amount of a compound for use in treating a disease or disorder in a subject. It is understood that the present invention provides a mesenchymal stem cell (MSC) and exosome therapeutic composition. Thus, in one aspect, a method for treating a disease or condition in an end-user subject is provided. Mesenchymal stem cell and exosome therapeutic compositions for use in treating disorders As disclosed herein, the compositions comprise a) a composition base and b) a composition suitable for use with the same hair type as the end user. type, hair color, hair type, skin type, skin color, race, and / or ethnicity , indicating that the donor is never afflicted by a disease or disorder suffered by the end user subject. Mesenchymal stem cells derived from donors with a single nucleotide polymorphism (SNP) profile The MSC and exosome preparations were used to investigate the mechanism of action of MSCs in normal hypertrophy. Cells or cell-conditioned medium cultured under oxygen culture conditions, and cultured under harsh wound healing conditions The cell culture medium comprises at least one member selected from the group consisting of cultured cells.

[0061] As discussed above, SNPs that distinguish between donors and recipients may be associated with a disease or disorder condition. It can result from SNPs associated with any number of related genes. In one embodiment, a mesenchymal stem cell and exosome therapeutic composition is disclosed herein, wherein the SNP is Interleukin 18 (IL-18) (e.g., rs1946518 and / or rs 187238, etc.), androgen receptor (AR) (e.g., Rs6152, Rs222 3841, and / or Rs2497938), histone deacetylase (HDAC) -4 (HDAC4) (e.g., Rs9287638, etc.), HDAC9 (e.g., Rs2 073963 and / or Rs2180439, etc.), paired box 1 (PAX1 ) (e.g. Rs1,160,312 and / or Rs6,047,844 etc.), FOXA2 (e.g. Rs1,160,312 and / or Rs60 47844), TAR DNA-binding proteins (TARDBPs) (e.g., Rs12 565727), autism susceptibility gene 2 (AUTS2) (e.g., Rs694554 1), SET-binding protein 1 (SETBP1) (e.g., Rs10502861, 17q21.31 (e.g., Rs12373124), tumor necrosis factor receptor seq. TNF-α family member 6B (TNFRSF6B) (e.g., Rs6010620, etc.) )), zinc finger CCCH type with G patch domain-containing proteins (ZG PAT) (e.g., Rs6010620, etc.), P2X purinergic receptor 7 (P2RX7) ( For example, Rs17525809, Rs28360447, Rs7958311, Rs17 18119, Rs2230912, Rs28360457, Rs2230911, and / or Rs1653624, etc.), oxytocin receptor (e.g., Rs237887, Rs2268491, Rs2254298, and / or Rs7632287, etc. Non-coding RNA (ncRNA) (e.g., Rs11669309, Rs2298075, and / or Rs10237038), long non-coding RNAs (lncRNAs) (e.g. For example, Rs8028149, Rs16868911, Rs11543230, Rs930 9325, Rs12951337, Rs15428265, Rs12683158, and and / or Rs6982502), human leukocyte antigen (HLA) (e.g., Rs226 9706, etc.), Platelet-derived growth factor (PDGF) receptor (PDGFR) B (PDGFR -B), tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP- 2, IL-23, activin A, intercellular adhesion molecule-2 (ICAM-2), osteopontin ( OPN), insulin, insulin growth factor binding protein 4 (IGF-BP4), tumor Tumor necrosis factor (TNF) receptor 1 (TNF-R1), ectodysplasin A2 receptor (Ectodysplasin A2 receptor) AR), and / or one or more of the genes encoding follistatin Contains the above SNPs.

[0062] In embodiments, the therapeutic composition comprises a base and MSCs, keratinocytes, and / or melanocytic cells. The MSC preparation (MSC / K / M / Prep) may comprise a cytoplasmic growth factor powder preparation. Cells or cell-conditioned medium cultured under normal hyperoxic culture conditions and harsh wound healing conditions The cell culture medium may comprise at least one member selected from the group consisting of cells cultured under conditions. Hyperoxic culture conditions can be defined as approximately 21%, which is the percentage of the total oxygen in the culture medium that is determined by serum supplements and acid. The wound healing conditions are 21%±5% oxygen with a high concentration of inflammatory cytokines. In the presence of angiogenic factors and / or reduced glucose, about 1 to about 5% oxygen and It can be defined as:

[0063] MSC / K / M / Prep is a conditioned medium or cell culture expanded MSC, keratinocyte In some embodiments, the lysate may include either lysates from cells or melanocytes. The composition may comprise about 0.01 to about 10% by weight of MSC / K / M / PREP or lineage cells. The medium may further comprise a cell-free medium conditioned by growth of the cells under normal hyperoxic culture conditions. The cells are cultured under normal or wound healing conditions.

[0064] MSC / K / M / PREP conditioned media, lysates, and derived products, or combinations thereof The combination may include emulsified lanolin alcohol, wax, and optionally other active ingredients. and oil mixtures, or petrolatum or mineral oils, quaternary ammonium compounds, fatty alcohols, A mixture of choline and fatty ester emollients or a lotion substantially similar in composition. The composition may be dissolved, mixed, or suspended in the solvent.

[0065] The base of the composition of the present disclosure may be a lotion, cream, pigment, serum, oil, gel, hydrogel, or the like. , powder, foundation, facial mask, lip care products, hair care products, hair Any suitable or desired base for care products, skin cleansers, peeling agents, ointments, injections, etc. Alternatively, the vehicle may be administered by direct injection into the subject or into any tissue, organ, or system of the subject. The adhesive may include any material suitable for direct application onto or through the adhesive.

[0066] In embodiments, the base is a mixture of emulsified lanolin alcohols, waxes, and oils, Contains petrolatum or mineral oil, quaternary ammonium compounds, fatty alcohols, and fatty esters. Alternatively, the base may comprise a lotion containing a mixture of emulsified lanolin and emollients. Alcohol, water, petrolatum, glycerin, isostearyl palmitate, butylene glycol The cream may include a mixture of glyceryl stearate, glyceryl stearate, or a mixture thereof. do.

[0067] In some embodiments, the cosmetic base may contain, for example, about 1 to about 20% by weight of a moisturizer, about 0. The carrier may contain 1 to about 10% by weight of a thickening agent and water. Alternatively, the carrier may contain about The carrier may comprise from about 70 to about 99% by weight of a surfactant, and from about 0 to about 20% by weight of a fat. , about 80 to 99.9% thickener, about 5 to 15% surfactant, about 2 to 15% moisturizer , about 0 to about 80% oil, very small amounts (less than 2%) of preservatives, colorants and / or fragrances, and may alternatively include water if desired.

[0068] In an embodiment, the composition further comprises a penetration enhancer to improve epidermal penetration of the biologically active agent. Suitable penetration enhancers include dimethyl sulfoxide (DMSO), DMSO-like compounds, The composition may also include glyceryl esters, ethanolic compounds, pyroglutamic acid esters, etc. It may contain sunscreens, anti-acne agents, anti-cellulite agents, and other additional ingredients.

[0069] The composition may be sterile filtered or concentrated. Additionally, the composition may contain no non-human animal products. The cellular components may be free of cellular components or may be derived from animal sources.

[0070] While the compositions are described above as including MSCs, the use of other fibroblast-like cells is also contemplated. It is envisaged that the product may contain keratinocytes or melanocytes. The MSCs may be It can be derived from multiple sources, such as bone marrow stroma, fat, blood, dermis, periosteum, bone, and other tissues. In embodiments, the MSCs may be derived from the patient to whom the composition will be applied (autologous) or or from another individual (allogeneic). MSC / K / M / PREP collects conditioned medium or grown to increase the amount of cells for lysis, or The culture may be used fresh prior to incorporation into the indicated compositions.

[0071] Producing a therapeutic composition of the present disclosure begins with determining whether the target consumer is a person of a particular race, ethnicity, skin color, skin tone, or skin tone. Identifying skin types, eye color, and hair color, as well as hair loss characteristics, and ethnicity, skin color, skin type, eye color, and hair color, as well as alopecia characteristics from individuals with M Procuring SCs and exosomes and administering them to subjects using the procured MSCs and creating a topical and / or injectable treatment that

[0072] Thus, the final treatment composition can be customized for the end user based on hair characteristics. To use the hair and scalp treatment compositions of the present disclosure, a user may The composition may simply be applied topically to the scalp. Alternatively, the composition may be applied to the area affected by compaction. The administration can be done by direct injection into the dermis in the area of ​​​​the skin. For example, the dose administered may be a single dose of 0.1, 0.2, 0.25, 0.3, 0.4, 0.5, 0.6, 0.7, 0.75, 0.8, 0. 9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1. 9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 3.0, 3.5, 4.0, 4. 5, 5.0, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 , 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or The volume may be 100 mL or may be aliquoted over multiple injections. For example, a single The 1 mL volume can be divided into 0.1 mL injections. When multiple injections are given, each injection The volumes are 0.1, 0.2, 0.25, 0.3, 0.4, 0.5, 0.6, 0.7, 0. 75, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1 .7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 3.0, 3 The injections can be in single doses of 0.5, 4.0, 4.5, 5.0, 6, 7, 8, 9, or 10 mL. As an injection site or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 , 14, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 1 60, 170, 180, 190, 200, 250, 300, 350, 400, 450, 5 Across 00, 600, 700, 800, 900, or 1000 separate injections, If multiple injections are used in the affected area, the distance between injections should be , 0.1, 0.2, 0.25, 0.3, 0.4, 0.5, 0.6, 0.7, 0.75, 0 .8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1 .8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 3.0, 3.5, 4 The distances can be 0.0, 4.5, 5.0, 6, 7, 8, 9, or 10 cm. However, it is also known that a single therapeutic administration may not be sufficient to achieve the desired therapeutic outcome. It is understood and contemplated herein. Thus, administration may be indicative of a therapeutic effect on the survival or duration of the host. Between, single or separate 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 6 5, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350, 400, Can occur 450, 500, 600, 700, 800, 900, or 1000 times. When multiple doses are administered, the doses are administered at 6, 12, 18, 24, 36, 48, 60, and 72 hours. , 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 3 5, 36, 42, 49, 56, 58, 59, 60, 61, 62, 9, 10, 11, 12 , 13, 14, 15, 16 weeks, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24 months , can occur once every 3, 4, 5, 6, 7, 8, 9, or 10 years.

[0073] The MSCs or similar fibroblast-like cells, keratinocytes, and keratinocytes used in the disclosed therapeutic compositions Concentrated growth factors, exosomes, extracellular Proteins, proteoglycans, cytokines, chemokines, proteins, and peptides It is understood and contemplated herein that the formulation may be diluted to arrive at the administered dose. The diluent may be saline or any pharmaceutical-based carrier or agent disclosed herein. The agent may be any suitable substance, including but not limited to an excipient. 1. Fibroblast-like cells, keratinocytes or melanocyte-derived growth factors, xosomes, extracellular proteins, proteoglycans, cytokines, chemokines, proteins The dilutions of proteins and peptides were 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, 1:25, 1:30, 1:35, 1: The ratio may be 1:40, 1:45, 1:50 or 1:100.

[0074] As reiterated throughout this disclosure, MSC and exosome therapeutic compositions are produced. The disclosed methods of producing the medicament are, in effect, a method for treating a disease or disorder (e.g., alopecia, alopecia) in a subject. Atopic dermatitis, autism spectrum disorder, multiple sclerosis, chronic pain, depression, anxiety, bipolar disorder Polar disorders, osteoporosis, rheumatoid arthritis, celiac disease, type II diabetes, coronary heart disease, hypertension The present invention relates to the treatment, inhibition, reduction, amelioration, prevention, and / or administration of any of the following drugs: The present invention provides a method for producing MSC and exosome therapeutic compositions that can be used in preventing and / or reversing Thus, in one aspect, the mesenchymal stem cells and exosomes disclosed herein are The present invention relates to a method for treating a disease or disorder in a subject, comprising administering to the subject any of the following therapeutic compositions: Harm (e.g., alopecia, atopic dermatitis, autism spectrum disorder, multiple sclerosis, chronic Pain, depression, anxiety, bipolar disorder, osteoporosis, rheumatoid arthritis, celiac disease, type II diabetes pulmonary circulation disorders, coronary heart disease, hypertension, multiple myelopathy, and / or cancer Methods of reducing, ameliorating, preventing, and / or reversing are disclosed herein.

[0075] The utility of exosomes as a carrier system for delivering gene correction has broad applicability. Essentially, the results are due to small sequence differences, e.g., single nucleotide polymorphisms (SNPs). Any genetic disease that results from this can be molecularly corrected via exosome incorporation into target cells. These molecules can be genetically modified Exosomes can be introduced from cell lines or individual cells carrying non-disease-related gene sequences. The cells may be procured from a donor.

[0076] The following examples of candidate SNPs associated with different disease states are provided for purposes of the invention as described. Provided as proof of concept, the present invention provides a method for delivering virtually any SNP correction sequence. may be used, and the scope of the utility of the present invention is not limited to the sequences listed below.

[0077] A number of SNPs have been reported to be associated with hair loss (alopecia). Table 1 shows the SNPs that occur List candidate SNPs and / or genes that are relevant to the present invention. [Table 1] [Table 2]

[0078] Systemic diseases may require delivery of the present invention via vascular routes (intravenous, intraarterial). Table 3 identifies examples of SNPs associated with diseases that may be optimally treated via a systemic delivery route. [Table 3]

[0079] For example, in one embodiment, a method for treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder is provided. Disclosed herein are methods for reversing the disease or disorder, wherein the disease or disorder is alopecia (e.g., androgenetic alopecia). , androgenetic alopecia, alopecia areata, cicatricial alopecia, telogen effluvium, or female pattern hair loss ) and the single nucleotide polymorphism (SNP) associated with alopecia in the subject is SN P Rs6152, Rs2223841, Rs2497938, Rs1160312, 6 047844, Rs2180439, Rs2073963, Rs12565727, Rs 9287638, Rs6945541, Rs12373124, Rs10502861, Rs187238 and / or Rs1946518 or or SNPs include AR, PAX1, FOXA2, TARDBP, HDAC4, HDAC9, AUTS2, 17q21.31, SETBP1, IL18, platelet-derived growth factor (PDG F) Receptor (PDGFR) B (PDGFR-B), tissue inhibitor of metalloproteinase (T TIMP-1 (TIMP-1), TIMP-2, IL-23, activin A, cell-cell adhesion molecule ICAM-2, osteopontin (OPN), insulin, insulin growth factor binding Integrative Growth Factor-BP4 (IGF-BP4), Tumor Necrosis Factor (TNF) Receptor 1 (TNF-R1) , ectodysplasin A2 receptor (XEDAR), and / or follistatin To connect.

[0080] In one embodiment, the method comprises administering to a subject a compound that is capable of treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder. Disclosed herein are methods for treating autism, wherein the disease or disorder includes autism spectrum disorder, The SNPs associated with spectrum disorders were SNPs Rs237887, Rs2268491 , Rs2,254,298, and / or Rs7,632,287.

[0081] Methods for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder are also provided herein. In accordance with the present disclosure, the disease or disorder includes osteoporosis, and the SNP associated with osteoporosis is S NP Rs28360447, Rs28360457, Rs1718119, Rs223 0911, and / or one or more of Rs1,653,624.

[0082] In one embodiment, the method comprises administering to a subject a compound that is capable of treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder. Disclosed herein is a method for treating rheumatoid arthritis, the disease or disorder comprising administering to the patient a therapeutically effective amount of ... Associated SNPs include SNP Rs2269706.

[0083] Methods for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder are also provided herein. The present disclosure relates to a method for treating multiple sclerosis, the method comprising: has one or more of the SNPs Rs17525809 and / or Rs28360447 Includes.

[0084] In one embodiment, the method comprises administering to a subject a compound that is capable of treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder. Disclosed herein is a method for treating a chronic pain syndrome, the method comprising administering to a patient a therapeutically effective amount of ... NP is one or more of SNPs Rs28360447 and / or Rs7958311 Including the above.

[0085] Methods for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder are also provided herein. The disease or disorder disclosed herein includes atopic dermatitis and is associated with atopic dermatitis. The SNPs involved include SNP Rs6010620.

[0086] In one embodiment, the method comprises administering to a subject a compound that is capable of treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder. Disclosed herein is a method for detecting a SNP associated with hypertension, the disease or disorder comprising: contains SNP Rs11669309.

[0087] Methods for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder are also provided herein. The disease or disorder includes coronary heart disease, and the SNP associated with heart disease is S Including NP Rs6982502.

[0088] In one embodiment, the method comprises administering to a subject a compound that is capable of treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder. Disclosed herein is a method for treating type II diabetes, wherein the disease or disorder comprises type II diabetes, Associated SNPs include SNP Rs12683158.

[0089] Methods for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder are also provided herein. The disease or disorder disclosed herein includes celiac disease, and SNPs associated with celiac disease contains SNP Rs15428265.

[0090] In one embodiment, the method comprises administering to a subject a compound that is capable of treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder. Disclosed herein is a method for detecting the disease or disorder anxiety, and the SNPs associated with anxiety are P Including Rs1718119.

[0091] Methods for treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder are also provided herein. The disease or disorder includes bipolar disorder, and the SNP associated with bipolar disorder is S Including NP Rs2230912.

[0092] In one embodiment, the method comprises administering to a subject a compound that is capable of treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder. Disclosed herein is a method for detecting a SNP associated with depression, the disease or disorder comprising: contains SNP Rs8028149.

[0093] Treating, inhibiting, reducing, ameliorating, preventing, and / or treating a disease or disorder of any of the preceding aspects. Also disclosed herein is a method of reversing a disease or disorder comprising identifying an individual with SNP Rs16868911 , Rs11,543,230, Rs9,309,325, and / or Rs12,951,337 Contains one or more of the following:

[0094] As mentioned above, the disclosed treatments are directed to any disease in which uncontrolled cell proliferation occurs, such as cancer. Thus, the present invention relates to a method for treating, inhibiting, reducing, ameliorating, or preventing a disease or disorder. Also disclosed herein are methods of improving, preventing, and / or reversing the disease or disorder, wherein the disease or disorder is cancer. Representative, but non-limiting, lists of cancers that the disclosed compositions can be used to treat include: The diseases are: lymphoma, B-cell lymphoma, T-cell lymphoma, mycosis fungoides, Myeloid leukemia, bladder cancer, brain cancer, nervous system cancer, head and neck cancer, squamous cell carcinoma of the head and neck, Lung cancer, including small cell lung cancer and non-small cell lung cancer, neuroblastoma / glioma ovarian cancer, skin cancer, liver cancer, melanoma, squamous cell carcinoma of the oral cavity, throat, larynx, and lung , cervical cancer, cervical carcinoma, breast cancer, as well as epithelial cancer, kidney cancer, genitourinary tract cancer, and lung cancer (p ulmonary cancer), esophageal carcinoma, head and neck carcinoma, colorectal cancer, hematopoietic organ cancer, testicular cancer , colon cancer, rectal cancer, prostate cancer, or pancreatic cancer. Thus, in one embodiment, the method of treating or inhibiting cancer is Disclosed herein are methods for reducing, ameliorating, preventing, and / or reversing the progression of cancer, wherein the cancer is pancreatic cancer. In one aspect, the present invention provides a method for treating, inhibiting, reducing, ameliorating, preventing, and / or preventing a disease or disorder. Disclosed herein are methods for reversing and / or treating breast cancer in a subject, wherein the disease is breast cancer. Associated SNPs include SNP Rs2298075. Methods of treating, inhibiting, reducing, ameliorating, preventing, and / or reversing harm are also disclosed herein. , the disease is pancreatic cancer, and the SNP associated with pancreatic cancer in the subject is SNP Rs10237 Includes 038.

[0095] Alopecia Hair is made of a protein called keratin. It sits in the hair follicle and is located at the base of the follicle. The average scalp contains stem cells called hair follicle epithelial stem cells that stimulate the production of new hair. The scalp contains over 100,000 hair follicles, each of which undergoes repeated cycles of producing hair and then resting. The hair growth and resting cycle is normal, and it is important to have hair all over your head at all times. bring about.

[0096] Alopecia occurs when more and more hair follicles are in the resting phase, or no longer producing new hair. Men who are destined to suffer from alopecia due to genetic characteristics should take the test. Hair follicles that are overly sensitive to the effects of dihydrotestosterone (DHT), a by-product of testosterone DHT binds to hair follicles and causes them to shrink. More and more hair follicles This process shrinks until the hair follicles no longer produce hair, causing areas to thin and eventually develop alopecia. This is called miniaturization.

[0097] Currently, the only drugs approved by the FDA to treat hair loss are minoxidil and and finasteride. Minoxidil is available as an over-the-counter topical medication. However, most experts agree that minoxidil is relatively effective in combating hair loss. It is agreed that the drug is a limited agent and has no effect on the miniaturization process. Finasteride blocks testosterone from becoming DHT. It works by inhibiting the hormone acetylcholinesterase, but its side effects include erectile dysfunction and impaired libido and ejaculation. Low-level laser therapy has been shown to stimulate hair growth in both men and women. However, this has no effect on miniaturization.

[0098] Hair transplantation is another way to treat hair loss, and involves growing hair from the back of the head that is DHT resistant. It involves harvesting hair follicles and transplanting them into the areas of alopecia. still have the same amount of hair, it's just redistributed more evenly across the scalp. , but does not stimulate new growth. What is needed is a drug that can both prevent and treat alopecia. The present invention relates to a composition and method for the treatment of hair follicle epithelial stem cells and It promotes the stimulation of mesenchymal stem cells and activates hair follicles to produce hair and prevent miniaturization.

[0099] Some embodiments of the present disclosure demonstrate that the donor never experiences hair loss. Mesenchymal stem cell (MSC) exons were isolated from targeted donors with specific SNP hair characteristics. Methods for preventing and treating alopecia, including preparing a secretome and a secretome concentrate The donor may be gender specific. The method includes a method for producing a composition for Identifying target donors based on SNP hair characteristics and culturing MSCs from the target donors We used 100% ethanol to prepare culture media under either normal hyperoxic culture conditions or harsh wound-healing hypoxic conditions. and preparing a powder from the culture medium. The powder is then mixed with a cream base or lotion. and combining the final product with a polyamide base, the final product being in the area affected by the miniaturization. The application can be either topical or injectable, particularly In areas affected by miniaturization or by direct injection into the dermis, hair follicle activation is improved. It can stimulate genitalia and promote hair growth.

[0100] Injected into the scalp in affected areas of subjects with male pattern baldness or androgenetic alopecia When this treatment was performed, successful hair regrowth was observed just 2 weeks after treatment (see Figures 2A-2E). .

[0101] Exosome suspensions generated using the methods and parameters described herein Proteomic assessment of the compounds may be performed to identify those that contribute to the clinically relevant efficacy of the described invention. The molecular composition of the chromatin was characterized. Proteomic evaluation was performed using a commercially available RayBio Tech (Norc We used an antibody array manufactured by Ross, GA, USA. either secreted, transported, or present on the outer surface of the cell membrane The concentrations of 230 different proteins known to be circulating in the blood were measured. It was found to be present in biologically relevant concentrations and to be associated with hair repair and coloration. The proteins measured are listed in Table 4. Physiologically relevant concentrations are defined as 1 pg / mL. Proteins with an average concentration of >50ug / mL were considered to be A literature search was performed to identify the most likely candidate molecules supporting clinical efficacy. Table The list in 4 is of individual proteins found within the present invention that are associated with beneficial effects. should not be considered a comprehensive or exhaustive list. [Table 4]

[0102] Proteins are ordered from highest to lowest average concentration. Proteins expressed at concentrations above any value of L were searched using the PubMed search engine. The medical literature was searched to identify studies that provide evidence for the potential efficacy of the present invention. The tannins of the present invention, which have been supported in the scientific literature as playing a role in hair follicle regeneration, The proteins are listed and described below.

[0103] IL18 was the most enriched protein present in the exosome suspension samples. Its main function is to regulate the innate immune response in the skin, specifically interferon It stimulates gamma production and activates natural killer cells and TH1 T cells in the dermis. Excessive IL18 is associated with the development of autoimmune diseases. A literature review also reveals its role in hair growth. We provide evidence for two single nucleotide variants found within the IL18 gene sequence. A single nucleotide polymorphism (SNP) is associated with the onset of alopecia areata (AA), an organ-specific autoimmune disease. Two specific SNPs, rs1946518 (-607C>A) and rs The 187238 (-137G>C) polymorphism is associated with the disease alopecia areata. reported that the IL-18 SNPs rs187238 and rs1946518 were associated with AA susceptibility. It was concluded that this could be the cause. 1 IL18 interacts with perifollicular mast cells and CD8+ cells. These interactions may play a role in the anomalous interactions observed between hair follicles. It may disrupt the normal hair growth cycle in the follicle. Histological analysis revealed that IL18 and its receptors is found in skin keratinocytes and in the outer root sheath cells of hair follicles. Two possible effects of IL18 action in initiating hair growth observed when applied to the The sequence of IL18 from the donor does not have a disease-associated sequence and IL18 signaling levels Alternatively, it may function as an autocrine inhibitor, altering the levels of There is evidence for IL18 isoforms, including the predominant form in serum that can be obtained by immunohistochemistry. This form of IL18 reduces IL18 signaling and promotes appropriate levels of innate immune responses. It may be an inhibitory isoform that restores the IL-1 signaling pathway.

[0104] Induction of the growth phase using conditioned medium from hypoxic adipose-derived mesenchymal stem / stromal cell populations It has been demonstrated that PDGF receptor B is the predominant protein detected, and PDGF , which can stimulate the proliferation of dermal papillae through the PDGF receptor. Exosome delivery of PDGF receptor B inhibits PDGF-mediated signaling that initiates anagen hair growth. Genetic variants in PDGFR-B may enable signal transmission. It is associated with alopecia in pediatric idiopathic rheumatoid arthritis.

[0105] Insulin growth factor is an agonist for hair growth. IGF binding protein is It regulates IGF activity by binding to various IGF-BPs. IGF-BP4 can modify GF activity and provide additional specificity to IGF activity. is expressed in the non-human hair follicle dermal papilla together with IGF-BP3 and IGF-BP5. , which plays a role in regulating IGF activity in the hair follicle.

[0106] Normal hair growth is cyclical. Each hair follicle undergoes extracellular remodeling throughout each cycle. TIMP-1 and TIMP-2 act as stimulators of the extracellular matrix in and around the hair follicle. Proteolytic activity of collagenases and other proteases involved in remodeling Additional TIMPs provided by the present invention play an important role in regulating , to balance the levels of proteases altered by inflammatory disease states associated with alopecia. This can repair the problem.

[0107] Interleukin 23 is found in hair follicles at higher levels during alopecia areata, Its exact function within the hair follicle remains unclear. Like other cytokines, IL23: Multiple functions depending on the isoform and the receptor expressed by different cell types The additional IL23 provided by the present invention may have inflammatory properties that result in hair growth inhibition. These compounds may provide an autocrine inhibitory signal that helps reduce the onset of inflammatory bowel disease.

[0108] Activin is a member of the TGF-B signaling pathway and mediates the early formation of developing hair follicles. They are important for the formation of hair follicles, and they mediate the epidermal / mesenchymal interactions required during hair organogenesis. In combination with follistatin, activin plays an important role in the hair cycle. It is an important regulator of

[0109] ICAM functions to connect and create a barrier between cells. Hair follicles are immune privileged. ICAM is an organelle that establishes a physical barrier that establishes an immune-privileged environment. In alopecia areata, the body develops an autoimmune response against antigens in melanocytes, which provide hair color. By providing ICAM-2, the present invention , which may allow the re-establishment of an immune-privileged microenvironment.

[0110] Osteopontin is expressed by the outer root sheath cells of the hair follicle. In vivo, FGF-7 production by outer root sheath keratinocytes is proteolytically cleaved Produces peptide signaling molecules that regulate life. Osteopontin-derived peptides appears to inhibit FGF-7 synthesis, which in turn slows hair growth. Pontin may be an important regulator of the hair growth cycle.

[0111] EDAR and XEDAR are members of the ectodysplasin family, Eda XEDAR binds to Eda A1 and Eda A2. XEDAR activates the NFKB signaling pathway. It is involved in signal transduction during hair follicle morphogenesis. The knockout study results in hair follicle malformation.

[0112] Mesenchymal stem cells As noted throughout, the therapeutic compositions disclosed herein are directed to mesenchymal stem cells ( Exosomes and / or growth factors derived from bone marrow concentrates or MSCs can be used. The study was carried out using adipose-derived stromal vascular cells (SVF) or various live cells from the umbilical cord, placenta, or amniotic membrane. The existing autologous and allogeneic MSCs contained within the post-product, expanded MSC cultures, It is currently used to treat a variety of conditions, including orthopedic and spinal conditions, and existing treatments include: A large amount of MSC secretome (growth factors, cytokines, chemokines, exosomes, cells (including, but not limited to, exosporins, exovesicles, and / or extracts). Stem cell-based treatments (including injectable treatments) can help prevent aging, scarring, and uneven pigmentation. It can help treat existing skin products such as creams, lotions, serums, and makeup. Despite evidence in the art that it is possible to treat and strengthen the skin, While other topical products contain ingredients that potentially help with In particular, it does not contain human MSCs or MSC-derived growth factors and proteins. Prior to the present disclosure, active MSC growth factor products that could be used for these applications had not been developed. Thus, in one aspect, the present invention is directed to treating wounds, orthopedic disorders, orthopedic injuries, ophthalmology, spinal cord, MSC secretome composition (MSC augmentation) for use in the treatment of spinal cord injury or spinal cord disorders Extracellular vesicles containing growth factors, MSC exosomes, MSC extracts, and / or compositions. The therapeutic compositions disclosed herein include, but are not limited to, (i) mesenchymal stem cells. (ii) a powdered additive of growth factors comprising a mesenchymal stem cell (MSC)-derived preparation; and The pharmaceutical composition includes a physiologically acceptable carrier.

[0113] As mentioned above, MSCs can give rise to a number of cell types, including myocytes, chondrocytes, adipocytes, and osteoblasts. These cells are pluripotent cells that have the ability to differentiate into any cell type. Typically, these cells are derived from blood It may be found in the placenta, umbilical cord blood, adipose tissue, bone marrow, or amniotic fluid, including peritubular tissue. As used herein, "MSC" refers to multipotent stem cells, multipotent stromal cells, stromal vascular cells, cells, pericytes, pericytes, stromal cells, pluripotent cells, multipotent cells, adipose-derived fibroblasts adipose-derived stromal vascular cells, adipose-derived MSCs, bone marrow-derived fibroblast-like cells, bone marrow derived stromal vascular cells, bone marrow derived MSCs, tissue derived fibroblast-like cells, adult stem cells, adult human including, but not limited to, stromal cells, keratinocytes, and / or melanocytes; Refers to non-terminally differentiated cells.

[0114] In addition to their differentiation potential, MSCs possess the ability to secrete many different cytokines and growth factors. It has long been recognized that the immune system has the immune-modulating ability to induce expression. When used herein, an "MSC preparation" or "MSC secretome composition" refers to a composition that is a mixture of human MSCs, fibroblasts, and / or fibroblasts. Blast-like cells, as well as horse, cow, pig, sheep, non-human primate, dog, cat, rabbit Non-human animal MSCs, including but not limited to MSCs from mice, rats, and mice MSC growth factors, MSC exosomes, extracellular vesicles, or acellular MSCs derived from In an embodiment, the composition comprises an extract or lysate of MSCs. Can be derived from the patient to whom it will be applied (autologous) or from another individual (allogeneic) MSCs can be cultured to recover conditioned medium or to increase the amount of cells in the lysate. They may be grown in culture or used fresh prior to incorporation into the compositions of the present disclosure.

[0115] MSC secretome composition (MSC growth factors, MSC exosomes, MSC extracts, and and / or extracellular vesicles containing the composition) is about 0.01 About 0.00001 to about 20% by weight, such as about 10% by weight, of mesenchymal stem cell (MSC) extract The MSC preparation may comprise an MSC product, an MSC exosome, or an MSC growth factor preparation. may contain either MSC conditioned medium or MSC lysate from cell culture expanded MSCs In some embodiments, the composition comprises about 0.01 to about 10% by weight of MSCs or MS The cell-free medium may further comprise a cell-free medium conditioned by proliferation of lineage C cells, the cells being The cells are cultured under oxygen culture conditions or artificial wound healing conditions.

[0116] As disclosed herein, the disclosed MSC additives (frozen or powdered additives) The MSCs used to generate the secretome composition of any of the growth factors MSC growth factors, secretome, cytokines, chemokines, mesenchymal stem cell proteins Proteins, peptides, glycosaminoglycans, extracellular matrix (ECM), proteoglycans The present invention relates to a method for the production of exosomes, secretomes, and exosomes. As used herein, MSC growth factor is a prostaglandin E2 (PGE2), transmembrane Transforming growth factor β1 (TGF-β1), hepatocyte growth factor (HGF), stromal cell-derived De novo factor-1 (SDF-1), nitric oxide, indoleamine 2,3-dioxygenase, Interleukin-4 (IL-4), IL-6, Interleukin-10 (IL-10) , IL-1 receptor antagonist and soluble TNF-α receptor, insulin-like growth factor , fibroblast growth factors (FGF) 1 to 23 (especially FGF1 and FGF2), bone formation factors BMP 1-15, epidermal growth factor (EGF), transforming growth factor -α (TGF-α), macrophage-stimulating protein (MSP), platelet-derived growth factor (P LGF), vascular endothelial growth factor (VEGF), macrophage colony-stimulating factor (M-CS F), insulin, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony hormones, including GM-CSF, as well as estrogen and thyroid hormones This includes, but is not limited to:

[0117] In one embodiment, the MSC preparation (such as, for example, an MSC secretome composition) is prepared using standard MSCs cultured under oxygen culture conditions (e.g., 21% oxygen) or artificial wound healing conditions In the presence of (e.g., inflammatory cytokines, angiogenic factors, and reduced glucose MSC growth factors, MSCs obtained from MSCs cultured in an environment with 0.1% to about 5% oxygen, etc. The present invention relates to a method for producing a cell-derived cellular extract of a human MSC comprising the steps of:

[0118] As disclosed herein, artificial wound healing conditions include reduced nutrient supply and local In actual wounds, where there is reduced waste removal usually caused by disruption of blood circulation, This simulates the growth conditions in the blood vessels that create new blood vessels and restore blood circulation. Therefore, the cells used to culture MSCs The artificial wound healing conditions used are the following growth conditions: reduced glucose availability, reduced oxygen tension, The modifications may include one or more of: reducing the concentration of nitrile, reducing the pH, and increasing the temperature.

[0119] In one aspect, glucose utilization may be reduced compared to a normal control. Modified culture media that reduce glucose levels but do not damage cells are preferred, with 0-50% reduction in glucose being the more preferred. For example, the reduction in glucose levels may be about 5% to 40%. The recovery culture conditions are about 5% to about 15%, about 10% to about 20%, about 15% to about 25%, and about 20%. about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 , 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 2 0, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 , 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, The glucose reduction may include 47, 48, 49, or 50%.

[0120] In one embodiment, the oxygen partial pressure can be reduced to hypoxic conditions. Normal atmospheric oxygen is approximately 21% Any reduction is considered hypoxic. Thus, in one embodiment, MSCs are artificially Under optimal wound healing conditions, oxygen concentrations of 0.0% to 20.9%, about 0.1% to about 0.5%, and about 0.1% to about 2.0%, about 0.1% to about 5.0% oxygen, about 0.5% to 5.0%, about 1. 0% to about 10% oxygen, about 5.0% to about 10.0% oxygen, and about 10.0% to about 15 Preferably, the MSCs may be cultured at 0.0% oxygen tension during culture to heal the condition. For example, 0, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7 , 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7 , 1.7, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7 , 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7 , 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7 , 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7 , 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7 , 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7 , 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7 , 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7 , 9.8, 9.9, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5 , 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5 , 19, 19.5, 20, or 20.5% oxygen, etc. It is raw.

[0121] The pH can also be reduced under artificial wound healing conditions. Physiological pH is very strictly maintained. The pH is usually very close to neutral, 7.2±0.2 (7.0-7.4). In the wound, the acidic environment is pH = 6.2 ± 0.2 (i.e., 6.0 to about 6.4). Thus, under artificial wound healing culture conditions, the pH can be 6.0, 6. 1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7. 6.0 to about 7.4, such as 6.0 to about 6.1, 7.2, 7.3, or 7.4 .4, 6.2 to 6.4, 6.2 to 6.6, 6.4 to 6.6, 6.4 to 6.6 .8, or from about 6.6 to about 7.0.

[0122] Under artificial wound healing culture conditions, the temperature of the culture environment was increased by 100%. Physiological homeostasis is maintained at 37°C (98.6°F). Small increases or decreases can cause significant changes in cell metabolism. By adding heat, you can increase the temperature above 37°C up to any temperature up to about 40°C (104°F). The temperature can create a "thermogenic" environment. Thus, in one embodiment, the artificial growth of MSCs Typical wound healing culture conditions are about 35°C to about 39°C, about 35°C to about 36°C, about 36°C to about 37°C, and about 38°C to about 40°C. ℃, about 37℃ to about 38℃, about 38℃ to about 39℃, about 39℃ to about 40℃ In one embodiment, the temperature of the artificial wound healing culture is 35.0, 35.1, 35.2, 35. 3, 36.4, 35.5, 35.6, 35.7, 35.8, 35.9, 36.0, 36. 1, 36.2, 36.3, 36.4, 36.5, 36.6, 36.7, 36.8, 36. 9, 37.0, 37.1, 37.2, 37.3, 37.4, 37.5, 37.6, 37. 7, 37.8, 37.9, 38.0, 38.1, 38.2, 38.3, 38.4, 38. 5, 38.6, 38.7, 38.8, 38.9, 39.0, 39.1, 39.2, 39. 3, 39.4, 39.5, 39.6, 39.7, 39.8, 39.9, or 40.0°C It could be.

[0123] The combined reduced nutrient and metabolic environment (artificial wound healing) New molecules such as glycosaminoglycans (GAGs), as well as growth factors and cytokines The wound healing and vascularization pathways that exist to induce tissue healing may be in the form of novel ECM proteins. The cultures were designed to produce anti-inflammatory and anti-inflammatory ECM proteins and growth factors as well as extracellular vesicles. Therefore, cell confluency, culture medium supplements, , nutritional supplements, oxygen levels, length of culture under those conditions, cell passage number, or By adjusting the cell growth conditions, such as their combination, MSCs can express the desired antibodies. Inflammatory proteins, peptides, cytokines, chemokines, glycosaminoglycans, extracellular Selectively targeting matrix (ECM), proteoglycans, exosomes and secretome It is understood and contemplated herein that the IL-1 protein may be stimulated to secrete IL-1 into the blood.

[0124] In one embodiment, temperature, oxygen tension, pH, glucose saturation, confluency, and growth rate are measured. Growth conditions, such as the growth surface, affect gene expression and protein production of cells growing in culture. It can affect the different growth factors and cytokines being produced. It is understood and contemplated herein that the growth surface stiffness can be achieved by, for example, The Young's modulus of the matrix affects gene expression and protein production in cells grown on it. Adipocytes and chondrocytes usually prefer a softer, more elastic growth surface (approximately 10k Pa to 12 kPa, whereas bone cells are maintained on hard surfaces (approximately 10 6 ~12 6 kP a) Cells grow better on the substrate. By adjusting the surface stiffness, the secretome and and their communication signals (growth factors, exosomes, cytokines, and It is possible that the receptors for inflammatory cytokines (e.g., inflammatory bowel disease and chemokines) may be affected.

[0125] In one embodiment, the MSC secretome composition (MSC growth factors, MSC exosomes, MSC C. extract and / or composition (including, but not limited to, extracellular vesicles containing the composition) To reduce degradation of growth factors, protective coating agents (e.g., cryoprotectant oligosaccharides and The protective coating may further comprise a polymer and a protein solution. It is understood and contemplated herein that a polymer may be manipulated in a manner that is relatively high molecular weight. It refers to a natural or synthetic organic compound of molecular weight whose structure consists of small repeating units called monocyclic aromatic compounds. Non-limiting examples of polymers include polyethylene, rubber, cellulose, Synthetic polymers are typically formed by addition or condensation polymerization of monomers. The term "copolymer" refers to a polymer formed from two or more different repeating units (monomer residues). By way of example and without limitation, copolymers include alternating copolymers, run copolymers, and the like. It may be a duplex copolymer, a block copolymer, or a graft copolymer. In some embodiments, the various block segments of the block copolymer may themselves comprise copolymers. It is also contemplated that the term "polymer" can be used to refer to any natural polymer, synthetic polymer, or polymeric material. Including, but not limited to, monopolymers, heteropolymers or copolymers, addition polymers, etc. In one embodiment, the gel matrix is ​​a copolymer. block copolymers, diblock copolymers, and / or triblock copolymers. It may contain mers.

[0126] In one aspect, the protective coating can include a biocompatible polymer. In some cases, the biocompatible polymer may be crosslinked. Rimers are polysaccharides; hydrophilic polypeptides; poly-L-glutamic acid (PGS), gamma- Polyglutamic acid, poly-L-aspartic acid, poly-L-serine, or poly-L-lysine Poly(amino acids) such as glycan; polyethylene glycol (PEG), polypropylene glycol polyalkylene glycol (PPG), and poly(ethylene oxide) (PEO) Alkyl and polyalkylene oxides; Poly(oxyethylated polyols); Poly(oxyethylated polyols); olefin alcohol; polyvinylpyrrolidone; poly(hydroxyalkyl methacrylate) Amides; Poly(hydroxyalkyl methacrylates); Poly(saccharides); Poly(hydroxy poly(vinyl alcohol), poly(lactic acid), poly(glycolic acid), and poly Polyhydroxy acids such as (lactic acid-co-glycolic acid); poly 3-hydroxybutyrate; or polyhydroxyalkanoates such as poly(4-hydroxybutyrate); Poly(lactides);Poly(orthoesters);Polyanhydrides;Poly(phosphazenes);Poly(lactides -co-caprolactone); polycarbonates such as tyrosine polycarbonate; polyamide Polyamides (including synthetic and natural polyamides), polypeptides, and poly(amino acids); Esteramides;Polyesters;Poly(dioxanone);Poly(alkylene alkylates) );Hydrophobic polyether;Polyurethane;Polyetherester;Polyacetal;Poly Cyanoacrylate;Polyacrylate;Polymethylmethacrylate;Polysiloxane; Poly(oxyethylene) / poly(oxypropylene) copolymers; Polyketals; Polylysine Polyalkylene oxalates;Polyalkylene succinates;Polyhydroxyvalerates;Polyalkylene oxalates;Polyalkylene succinates poly(maleic acid), as well as copolymers thereof. Biocompatible polymers also include polyamides, polycarbonates, polyalkylenes, poly Alkylene glycol, polyalkylene oxide, polyalkylene terephthalate (po lyalkylene terepthalate), polyvinyl alcohol (PVA) , methacrylate PVA (m-PVA), polyvinyl ether, polyvinyl ester, poly Polyvinyl halides, polyvinylpyrrolidone, polyglycolide, polysiloxane, poly Urethanes and their copolymers, alkyl celluloses, hydroxyalkyl celluloses cellulose, cellulose ethers, cellulose esters, nitrocellulose, acrylic and methacrylic Polymers of acrylic esters, methylcellulose, ethylcellulose, hydroxypropyl Cellulose, Hydroxypropylmethylcellulose, Hydroxybutylmethylcellulose Cellulose acetate, cellulose propionate, cellulose acetate butyrate cellulose acetate phthalate, carboxyethyl cellulose, cellulose triacetate acetate, sodium cellulose sulfate, poly(methyl methacrylate), poly Poly(ethyl methacrylate), Poly(butyl methacrylate), Poly(isobutyl methacrylate) poly(hexylmethacrylate), Poly(isodecyl methacrylate), Poly(lauryl methacrylate), Poly(phenyl Poly(methacrylate), poly(methyl acrylate), poly(isopropyl acrylate), Poly(isobutyl acrylate), poly(octadecyl acrylate), polyethylene, Polypropylene, poly(ethylene glycol), poly(ethylene oxide), poly(ethylene Poly(vinyl terephthalate), poly(vinyl alcohol), poly(vinyl acetate), polychlorinated Vinyl polystyrene and polyvinylpyrrolidone idone), their derivatives, their linear and branched copolymers and block copolymers Exemplary biodegradable polymers include polyesters, polyester polymers, and mixtures thereof. , poly(orthoester), poly(ethyleneamine), poly(caprolactone), poly( hydroxybutyrate), poly(hydroxyvalerate), polyanhydrides, poly(acrylic acid), polyglycolide, poly(urethane), polycarbonate, polyphosphate ester, poly Riphospriazenes, their derivatives, their linear and branched copolymers and block copolymers copolymers, as well as mixtures thereof.

[0127] In some embodiments, the protective coating comprises a carbohydrate structure of monosaccharides, as well as non-saccharides. Disaccharides or polysaccharides, including but not limited to reducing polysaccharides or disaccharides The protective coating agent may include any of the carbohydrate polymers, as well as any combination thereof. Examples of carbohydrates that can be used in the synthesis include glucose, aldoses (D-allose, D-altose, etc. glycerol, D-mannose, etc.), glucopyranose, pentahydroxyhexanal, α -D-Glucopyranosyl-D-glucose, α-D-glucopyranosyl-dihydrate, β- Polymers of D-glycopyranosyl units, β-D-fructofuranosyl α-D-glucopyranosyl D-galactopyranosyl-D-glucose, α-D-galactopyranosyl-D-glucose, β-D-galactopyranosyl-D-glucose Glucopyranosyl-α-D-glucopyranoside (anhydrous / dihydrate), galactose, pentose intose (ribose, xylose, lyxose), dextrose, dodecacarbon monosaccharide Decahydrate, fructose, sucrose, lactose, maltose, trehalose, agarose D-galactosyl-β-(1-4)-anhydro-L-galactosyl, cellulose Glycosyl, polymers of β-D-glycopyranosyl units, and starch, as well as polyhydric alcohols. Alcohols, polyalcohols, alditols, erythritol, glycitol, glycerol, Includes sorbitol, sorbitol, and sorbitol.

[0128] In some embodiments, the protective coating is poly(lactic acid), poly(glycolic acid), ), and biocompatible and / or biodegradable poly(lactic-co-glycolic acid). The particles contain one or more of the following polyesters: Can include: homopolymers containing glycolic acid units, referred to herein as "PGA"; Poly-L-lactic acid, poly-D-lactic acid, poly-D,L, collectively referred to as "PLA" in the specification -lactic acid, poly-L-lactide, poly-D-lactide, and poly-D,L-lactide5 Homopolymers containing lactic acid units, as well as those collectively referred to herein as "PCL" Homopolymers containing caprolactone units, such as poly(e-caprolactone), as well as Collectively referred to herein as "PLGA," these polymers are characterized by a ratio of lactic acid:glycolic acid. Various poly(lactic acid-co-glycolic acid) and poly(lactide-co-glycolide) copolymers containing lactic acid and glycolic acid units and polyacrylates, such as of the form and derivatives thereof. Exemplary polymers are also referred to herein as "PEGylated polymers." Various forms of collectively referred to as PLGA-PEG or PLA-PEG copolymers , polyethylene glycol (PEG) and copolymers of the aforementioned polyesters. In certain embodiments, the PEG region is covalently associated with the polymer to provide a cleavable phosphoryl group. In one embodiment, the polymer can be at least At least 60, 65, 70, 75, 80, 85, 89, 90, 91, 92, 93, 94, 9 containing 5, 96, 97, 98, or 99 percent acetal pendant groups.

[0129] The triblock copolymers disclosed herein can be, for example, polyethylene glycol (PE G), polyvinyl acetate, polyvinyl alcohol, polyvinylpyrrolidone (PVP) , polyethylene oxide (PEO), poly(vinylpyrrolidone-co-vinyl acetate) , polymethacrylate, polyoxyethylene alkyl ether, polyoxyethylene castor Shiitake oil, polycaprolactam, polylactic acid, polyglycolic acid, poly(lactic-glycolic) acid, Poly(lactic-co-glycolic) acid (PLGA), hydroxymethylcellulose, hydroxypropyl The core polymers include cellulose derivatives such as propyl cellulose.

[0130] Diblock copolymers that may be used in the protective coatings disclosed herein Examples of the polyvinyl alcohol include polyethylene glycol (PEG), polyvinyl acetate, and polyvinyl acetate. Alcohol (PVA), Polyvinylpyrrolidone (PVP), Polyethylene oxide (PEO ), poly(vinylpyrrolidone-co-vinyl acetate), polymethacrylate, polyoxyethylene Diethylene alkyl ether, polyoxyethylene castor oil, polycaprolactam, poly Lactic acid, polyglycolic acid, poly(lactic-glycolic) acid, poly(lactic-co-glycolic) acid (P Polymers such as LGA.

[0131] In one embodiment, a protective coating can be included (i.e., encapsulated, The encapsulated composition may contain lecithin or hydrolyzed lecithin as a carrier or encapsulating material. As used herein, lecithin and / or hydrolyzed The lecithin coating agent is phosphatidylcholine, phosphatidylinositol, Contains phosphatidylethanolamine, phosphatidylserine, and phosphatidic acid The source of the lecithin may be pnat or animal source.

[0132] In one embodiment, the protective coating is formed by placing the MSC additive in an encapsulation solution. Among the polymers, monosaccharides, disaccharides, or polysaccharides used to form the coating agent Any of the above may be in a suitable concentration to form a protective coating. Polymers, monosaccharides, disaccharides, or polysaccharides can be used at any concentration between 0.01 mM and 10.0 M. For example, about 0.01M to about 0.1M, about 0.1mM to about 1.0M, about 1.0M to about 10 Exemplary concentrations are 0.01, 0.02, 0.03, 0.04, 0.0 5, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0. 4, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 2 0, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 1 40, 150, 160, 170, 180, 190, 200, 225, 250, 275, 3 00, 325, 350, 375, 400, 450, 500, 600, 700, 800, 9 00mM, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1 Includes .9, 2, 3, 4, 5, 6, 7, 8, 9, 10M.

[0133] As shown in Figures 1 and 2, the exosomes in the disclosed MSC secretome composition Microorganisms and extracellular vesicles have been produced.

[0134] In one embodiment, one method of treating a wound involves administering an MSC secretome composition (MSC proliferation factor). The present invention relates to a method for the preparation of a medicament for the treatment of cancer, the method comprising administering to a patient a therapeutically effective amount ... The administration of the agent may be by any of the following means: subcutaneous, intramuscular, intravenous, topical (e.g., saline), (e.g., through the use of intravenous, intravenous, intramuscular, intravenous ... through stents, sponges, matrices, scaffolds, bandages, etc. bandages, sutures, grafts, surgical drapes, surgical adhesives, and / or staples It is understood that the present invention is also based on the impregnation of the MSC secretome composition. As contemplated herein, in one embodiment, a therapeutically effective amount of an MSC secretome composition is Medicated stents, scaffolds, sponges, matrices, adhesive bandages, wound care products, Wound dressings, grafts, surgical drapes, sutures, ointments, creams, or wound adhesives are disclosed herein. As described above, the MSC secretome composition (MSC growth factors, MSC Exosomes, MSC extracts, and / or extracellular vesicles containing compositions, The compositions, including but not limited to, may be administered topically, such as to the face, neck, hands, or any other desired area of ​​the body. It can be applied to adhesive bandages, wound dressings, grafts, surgical drapes, sutures, scars, etc. When applied to a fold, matrix, sponge, or stent, MSC secretion The tome composition may be applied as a powder.

[0135] In one embodiment, the MSC secretome composition disclosed herein (MSC growth factors, MS C. Exosomes, extracellular vesicles containing MSC extracts and / or compositions, (not limited to) may be oils, waxes or other standard fatty substances, or conventional gelling agents. and / or thickening agents, emulsifiers, moisturizers, emollients, sunscreens, ceramides, etc. Water-based or lipophilic active agents, agents for combating free radicals, bactericides, sequestering agents, antiseptics Preservatives, basifying or acidifying agents, fragrances, surfactants, fillers, aloe or green tea extracts wound care products, such as natural products or extracts of natural products, vitamins, or colorants; It may contain any known ingredient typically found in the healing arts. Other ingredients may include antioxidants, which may be selected from a variety of antioxidants. Suitable Antioxidants Vitamin C (L-ascorbic acid, magnesium ascorbyl phosphate, palladium phosphate) Ascorbyl myristate, tetrahexyldecyl ascorbate, vitamin E (tocotrienol) enol), Vitamin A (retinol, retinal, retinoic acid, beta-carotene, etc. provitamin A carotenoid), N-acetylglucosamine, or glucosamine Contains other derivatives. Other ingredients include linoleic acid (LA), gamma-linoleic acid (GLA), Alpha-linoleic acid (ALA), dihomo-y-linolenic acid (DGLA), arachidonic acid At least one of the following fatty acids may be present: omega-3, omega-6, and omega-9 polyunsaturated fatty acids, such as ... It may contain one essential fatty acid. The fatty acid may be evening primrose oil, blackcurrant oil, borage oil, or It can be derived from a variety of sources, including GLA-modified safflower seeds. Other ingredients include N-acetylglucosamine, Glucosamine or other derivatives of glucosamine, ultra-low molecular weight (ULMW) hyaluronan Platelet-rich fibrin matrices, such as chondroitin sulfate, chondroitin sulfate, or keratin sulfate, The composition may comprise at least one component that supports the production of hyaluronic acid, ECM and hyaluronic acid.

[0136] The MSC secretome compositions disclosed herein are useful for rejuvenating, enhancing, and improving wound healing. It is understood and contemplated herein that the composition may provide improved or repaired skin tissue. The composition may also be used as an injection in the treatment of arthritis and degenerative discs. Embodiments of the composition include insulin, insulin-like growth factors, thyroid hormones, fibroblasts, and the like. Inclusion of additional growth factors or hormones, such as follicular growth factor, estrogen, or retinoic acid In some embodiments, the disclosed stem cell growth factor compositions may not require Antibiotics, Antiacne, Liposomes, Antioxidants, Platelet-rich Fibrin Matrix, Antibiotics Painkillers, anti-inflammatory drugs, as well as insulin, insulin-like growth factors, thyroid hormones, fibroblast growth factor receptors, and thyroid hormones. Additional growth factors, including but not limited to cellular growth factors, estrogen, and retinoic acid Such additional active ingredients may include additional active ingredients not disclosed herein. Stem cell growth factors and extracellular vesicle compositions as indicated, as well as MSC conditioned medium, MSC lysates , and MSC derived products, then emulsified lanolin alcohol, wax , and a mixture of oils, or petrolatum or mineral oil, a quaternary ammonium compound, a fat A mixture of alcohol and fatty ester emollients or a mixture of substantially similar compositions. The composition may be thawed or dissolved, mixed, or suspended in the solution.

[0137] 1. Pharmaceutical Carriers / Delivery of Pharmaceutical Products As described above, the composition is administered in vivo in a pharma- ceutically acceptable carrier. By "pharmacologically acceptable" it is meant that the compound is not biologically or otherwise undesirable. Materials, i.e., without causing or being affected by any undesirable biological effects. interact in a deleterious manner with any of the other components of the pharmaceutical composition in which it is included. A carrier refers to a material that can be administered to a subject together with a nucleic acid or vector, without the need for a carrier. As will be known to those skilled in the art, the active ingredient may be mixed in a manner that minimizes any degradation of the active ingredient and is suitable for application to a wide variety of applications. Naturally, this would be selected to minimize any adverse side effects in the setting.

[0138] The compositions may be administered orally, parenterally (e.g., intravenously), by intramuscular injection, intraperitoneally, By injection, transdermally, externally, topically, etc. (local intranasal administration or administration by inhalation) As used herein, "local intranasal administration" refers to either or both nostrils, and includes delivery of the composition to the nose and nasal passages by means of a spray mechanism or This may include delivery by a droplet mechanism or through aerosolization of the nucleic acid or vector. Administration of the composition by inhalation can be by nasal or intranasal administration via delivery by a spray or droplet mechanism. Delivery can be via the oral cavity or via intubation to any area of ​​the respiratory system (e.g. The exact amount of composition required will vary depending on the species of subject, Age, weight, and general condition, the severity of the allergic disorder being treated, the specific The nucleic acid or vector used, the mode of administration, etc. will vary from subject to subject. Thus, it is not possible to specify an exact amount for every composition. An appropriate amount can be determined by one of ordinary skill in the art using only routine experimentation given the teachings herein. can be determined by

[0139] Parenteral administration of the composition, if used, is generally characterized by injection. The agents may be in liquid solution or suspension, solid form suitable for solution of suspension in liquid prior to injection, or For parenteral administration, the formulation may be prepared in any conventional form, either as an emulsion or as a medicament for administration in a parenteral setting. A more recently revised approach is to use sustained release systems or involves the use of sustained release systems. See, for example, U.S. Pat. No. 3,633,663, which is incorporated herein by reference. See US Pat. No. 610,795.

[0140] The material may be in solution, suspension (e.g., incorporated into microparticles, liposomes, or cells). These are molecules that bind to specific cell types via antibodies, receptors, or receptor ligands. The following references provide information on targeting specific proteins to tumor tissue: This is an example of the use of this technique for bioconjugation (Senter, et al., Bioconjugation e Chem., 2:447-451, (1991), Bagshawe, K.D. Br.J.Cancer,60:275-281,(1989), Bagshawe, et al.,Br.J.Cancer,58:700-703,(1988),Sen ter, et al.,Bioconjugate Chem.,4:3-9,(19 93), Battelli, et al., Cancer Immunol. Immu nother.,35:421-425,(1992),Pietersz and M. cKenzie,Immunolog.Reviews,129:57-80,(199 2) and Roffler, et al., Biochem. Pharmacol. 42:2062-2065, (1991). "Stealth" and other antibody conjugates Tribosomes (including lipid-mediated drug targeting to colon carcinoma), cell-specific ligands Receptor-mediated targeting of DNA through endothelial cells, lymphocyte-specific tumor targeting, and in vivo A vehicle for highly specific therapeutic retroviral targeting of mouse glioma cells. The references are examples of the use of this technology to target specific proteins to tumor tissue. (Hughes et al., Cancer Research, 49:6214-6 220, (1989), and Litzinger and Huang, Biochi mica et Biophysica Acta,1104:179-187,(19 92) In general, receptors are expressed in endocytic cells either constitutively or ligand-induced. These receptors are clustered in clathrin-coated pits and mediate the cis pathway. They enter the cell via clathrin-coated vesicles and pass through acidified endosomes where they are sorted by receptors. They are then recycled to the cell surface, stored intracellularly, or transported to the lysosomes. The internalization pathway involves the uptake of nutrients, activation of proteins, or degradation of proteins in the tissue. Protein removal, macromolecule clearance, opportunistic entry of viruses and toxins, ligands They serve a variety of functions, including the dissociation and degradation of receptors, and the regulation of receptor levels. The signal transduction is determined by cell type, receptor concentration, type of ligand, ligand valency, and ligand binding activity. Depending on the concentration, they follow two or more intracellular pathways. The structure and cellular mechanisms of DNA synthesis have been reviewed (Brown and Greene, 2003). nd Cell Biology 10:6,399-409(1991)).

[0141] a) Pharmaceutically acceptable carrier The compositions containing the antibodies may be used therapeutically in combination with a pharma- ceutically acceptable carrier.

[0142] Suitable carriers and their formulations are described in Remington: The Science nd Practice of Pharmacy(19th ed.)ed.AR Gennaro,Mack Publishing Company,Easton,P A 1995. Typically, an appropriate amount of a pharma- ceutically acceptable salt is added to the formulation. Examples of pharma- ceutically acceptable carriers include saline, These include, but are not limited to, Ringer's solution, and dextrose solution. The pH of the solution is , preferably about 5 to about 8, more preferably about 7 to about 7.5. The matrix is ​​an antimicrobial agent in the form of a shaped article, e.g., a film, a liposome, or a microparticle. Sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the bodies. Certain carriers may be more preferred depending upon, for example, the route of administration and concentration of composition being administered. It will be apparent to one skilled in the art that there are cases where this is desirable.

[0143] Pharmaceutical carriers are known to those skilled in the art. They are most typically soluble in water at physiological pH. Standards for administration of drugs to humans, including solutions such as sterile water, saline, and buffer solutions The composition may be administered intramuscularly or subcutaneously. The drug will be administered according to standard procedures used by practitioners.

[0144] Pharmaceutical compositions may contain, in addition to the molecule of choice, carriers, thickeners, diluents, buffers, preservatives, The pharmaceutical composition may also include one or more of an antibacterial agent, an anti-inflammatory agent, an anesthetic agent, and the like. The above active ingredients may be included.

[0145] The pharmaceutical composition will depend on whether local or systemic treatment is desired and the area to be treated. Administration can be in several ways, depending on the individual. Administration can be local (ophthalmic, vaginal, rectal, nasal, Orally, by inhalation, or parenterally, e.g., by intravenous infusion, subcutaneous, abdominal The disclosed antibodies can be administered intravenously, intraperitoneally, intramuscularly, or intramuscularly. Administration may be intramuscular, subcutaneous, intracavity, or transdermal.

[0146] Preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents include propylene glycol, polyethylene glycol, oils such as olive oil, and injectable organic esters such as ethyl oleate Aqueous carriers include water, alcoholic / aqueous solutions, emulsions or suspensions. , saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer's Dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oil Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (Ringer's dextrose), For example, antibacterial agents, antioxidants, chelating agents, and Preservatives and other additives such as inert gases and the like may also be present.

[0147] Formulations for topical administration include ointments, lotions, creams, gels, drops, suppositories, sprays, etc. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners, Agents, etc. may be necessary or desirable.

[0148] Compositions for oral administration may be administered in water or non-aqueous media, capsules, sachets, or tablets. Includes powders or granules, suspensions or solutions. Thickeners, flavourings, diluents, emulsifiers, dispersing aids or A binder may be desirable.

[0149] Some of the compositions include hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfuric acid, , and inorganic acids such as phosphoric acid, as well as formic acid, acetic acid, propionic acid, glycolic acid, lactic acid , pyruvic acid, oxalic acid, malonic acid, succinic acid, maleic acid, and fumaric acid. By reaction with acids or with sodium hydroxide, ammonium hydroxide, or potassium hydroxide and inorganic bases such as mono-, di-, trialkyl and aryl amines, as well as substituted aryl amines. phenolamine, or other organic bases, which form pharma- ceutically acceptable acids or can potentially be administered as a base addition salt.

[0150] b) Therapeutic use Effective dosages and schedules for administering the compositions may be empirically determined, such It is within the skill of the art to make such a determination. Dosage ranges for administration of the compositions is sufficiently large to produce the desired effect in which the symptoms of the disorder are affected. The amount must not be so large as to cause undesirable cross-reactions, anaphylactic reactions, or other side effects. Generally, the dosage will depend on the age, condition, sex, and extent of the disease of the patient, the dosage of the The route of administration, or whether other drugs are included in the regimen, may vary by those of skill in the art. The dosage can be adjusted by the individual physician in the event of any contraindications. Dosage can vary and can be administered in one or more doses daily for one or several days. The guidance is based on literature recommendations regarding appropriate dosages for a given class of pharmaceutical product. For example, guidance for selecting an appropriate dose for an antibody can be found in Literature on the therapeutic use of, e.g., Handbook of Monoclonal Antibodies, Ferrone et al., eds., Noges Pub lications, Park Ridge, NJ, (1985) ch.22 an d pp.303-357, Smith et al., Antibodies in Human Diagnosis and Therapy,Haber et al. ,eds.,Raven Press,New York(1977)pp.365-3 A typical daily dosage for an antibody used alone will depend on the factors mentioned above. Depending on the dosage, doses range from about 1 μg / kg up to 100 mg / kg of body weight or more per day. It could be in the area.

[0151] The preceding examples will enable one of skill in the art to easily and readily identify the compounds, compositions, articles, and devices claimed herein. provide a complete disclosure and description of the methods and / or processes by which they are made and evaluated are shown as such and are intended to be purely illustrative and are not intended to limit the present disclosure. Although efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), Unless otherwise indicated, parts are by weight. The temperature is in °C or at ambient temperature, and the pressure is atmospheric or at its equivalent. It's nearby.

[0152] C. References Alam M, Bertolini M, Gherardini J, Kere n A, Ponce L, Cheret J, Alenfall J, Dune r P, Nilsson AH, Gilhar A, Paus R.An ost eopontin-derived peptide inhibits human hair growth at least in part by decreasi of fibroblast growth factor-7 production Br J in outer root sheath keratinocytes Dermatol.2019 Aversa A , Basciani S , Visca P , Arizzi M , Gnessi L, Frajese G, Fabbri A.Platelet- derived growth factor (PDGF) and PDGF re ceptors in rat corpus cavernosum: change s in expression after transient in vivo hypoxia.J Endocrinol.2001 Aug;170(2):395 -402. Batch JA, Mercury FA, ​​Werther GA.Ident ication and localization of insulin-like growth factor-binding protein (IGFBP) m There are essenger RNAs in human hair follicle mal papilla.J Invest Dermatol.1996 Mar;1 06(3):471-5. Bertolini M, Zilio F, Rossi A, et al.Abn ormal interactions between perifollicula r mast cells and CD8+ T-cells may contri bute to the pathogenesis of alopecia are ata.PLoS ONE.2014;9:e94260. Boraschi D, Dinarello CA.IL-18 in autoim munity: review.Eur Cytokine Netw.2006;17 :224-252.Fouad NA, Baraka EA, Hassan WA. Interleukin-18 gene polymorphisms in sys temic lupus erythematosus: relation to d isease status.Egypt J Immunol.2014;21:1- 12. Botchkarev VA, Fessing MY.Edar signaling in the control of hair follicle develop ment.J Investig Dermatol Symp Proc.2005 Dec;10(3):247-51.Celik SD, Ates O.Geneti c analysis of interleukin 18 gene polymo rphisms in alopecia areata.J Clin Lab An al.2018 Jun;32(5):e22386. Chen CC, Murray PJ, Jiang TX, Plikus MV, Chang YT, Lee OK, Widelitz RB, Chuong C M.Regenerative hair waves in aging mice and extra-follicular modulators follista tin, dkk1, and sfrp4.J Invest Dermatol.2 014 Aug;134(8):2086-2096. Chun Hou, Yong Miao, Xue Wang, Chaoyue C hen, Bojie Lin, Zhiqi Hu.Expression of m atrix metalloproteinases and tissue inhi bitor of matrix metalloproteinases in th e hair cycle Exp Ther Med.2016 Jul;12(1) :231-237.Published online 2016 May 9. Gilhar A.Collapse of immune privilege in alopecia areata: coincidental or substa ntial?J Invest Dermatol.2010 Nov;130(11) :2535-7. Kawabe TT, Rea TJ, Flenniken AM, William s BR, Groppi VE, Buhl AE.Localization of TIMP in cycling mouse hair.Development. 1991 Apr;111(4):877-9 Kim SK, Park HJ, Chung JH, et al.Associa tion between interleukin 18 polymorphism s and alopecia areata in Koreans.J Inter feron Cytokine Res.2014;34:349-353. McDowall M, Edwards NM, Jahoda CA, Hynd PI.The role of activins and follistatins in skin and hair follicle development a nd function.Cytokine Growth Factor Rev.2 008 Oct Dec;19(5-6):415-26. Park BS, Kim WS, Choi JS, Kim HK, Won JH , Ohkubo F, Fukuoka H.Hair growth stimul ated by conditioned medium of adipose-de rived stem cells is enhanced by hypoxia: evidence of increased growth factor sec retion.Biomed Res.2010 Feb;31(1):27-34Si valingam SP, Yoon KH, Koh DR, Fong KY.Si ngle-nucleotide polymorphisms of the int erleukin-18 gene promoter region in rheu matoid arthritis patients: protective ef fect of AA genotype.Tissue Antigens.2003 ;62:498-504. Suarez-Farinas M, Ungar B, Noda S, Shrof f A, Mansouri Y, Fuentes-Duculan J, Czer nik A, Zheng X, Estrada YD, Xu H, Peng X , Shemer A, Krueger JG, Lebwohl MG, Gutt man-Yassky E.Alopecia areata profiling s hows TH1, TH2, and IL-23 cytokine activa tion without parallel TH17 / TH22 skewing. J Allergy Clin Immunol.2015 Nov;136(5):1 277-87. Wang G, Dai D, Chen X, Yuan L, Zhang A, Lu Y, Zhang P.Upregulation of neuregulin -1 reverses signs of neuropathic pain in rats.Int J Clin Exp Pathol.2014 Aug 15; 7(9):5916-21. Wang X, Chen H, Tian R, Zhang Y, Drutska ya MS, Wang C, Ge J, Fan Z, Kong D, Wang X, Cai T, Zhou Y, Wang J, Wang J, Wang S, Qin Z, Jia H, Wu Y, Liu J, Nedospasov SA, Tredget EE, Lin M, Liu J, Jiang Y, Wu Y.Macrophages induce AKT / β-catenin-de pendent Lgr5(+) stem cell activation and hair follicle regeneration through TNF. Nat Commun.2017 Mar 27;8:14091.

Claims

1. Treating, inhibiting, reducing, ameliorating, preventing, and / or reversing a disease or disorder in a subject 1. A method for producing a mesenchymal stem cell and exosome therapeutic composition for a) identifying the end user's hair, skin color, skin type, race, and ethnicity; b) a single nucleotide polymorphism (SNP) associated with said disease or disorder in said subject; Identifying the c) having the same hair type, color, and / or ethnicity as the subject, but A single nucleotide polymorphism (SNP) profile that indicates that a person will never experience a disease or disorder obtaining mesenchymal stem cells (MSCs) from a targeted donor having the gene; d) preparing an MSC and exosome preparation from the obtained MSC, the MSC and exosome preparations contain corrective SNPs and cytokines; and and / or growth conditions sufficient to generate MSCs and exosomes that secrete them. and preparing the MSCs in a medium comprising the MSCs.

2. The method further comprises identifying the type and amount of growth factors in the MSC and exosome preparation. The method of claim 1 , further comprising: determining

3. The method of claim 2, wherein the growth factor is identified through proteomic analysis.

4. 2. The method of claim 1, further comprising characterizing the exosomal RNA. How to.

5. The method of claim 4, wherein the exosomal RNA is obtained by sequencing.

6. The disease or disorder is alopecia, atopic dermatitis, autism spectrum disorder, multiple myelopathy, Sclerosis, chronic pain, depression, anxiety, bipolar disorder, osteoporosis, rheumatoid arthritis, celiac disease , type II diabetes, coronary heart disease, hypertension, multiple coexisting diseases, and / or cancer; The method of claim 1.

7. The alopecia is male pattern baldness, androgenetic alopecia, alopecia areata, cicatricial alopecia, The method of claim 6, comprising terminal alopecia, or female pattern baldness.

8. 8. The method of claim 7, wherein the therapeutic composition stimulates hair follicle activation to promote hair growth. 。

9. The method of claim 6 , wherein the cancer comprises pancreatic cancer or breast cancer.

10. The SNP is an interleukin 18 (IL-18), an androgen receptor (AR), Histone deacetylase (HDAC)-4 (HDAC4), HDAC9, paired bock PAX1, forkhead box A2 (FOXA2), TAR DNA binding protein protein (TARDBP), autism susceptibility gene 2 (AUTS2), SET-binding protein SETBP1, 17q21.31, tumor necrosis factor receptor superfamily member Bar 6B (TNFRSF6B), zincfin with G-patch domain-containing protein ZGAR CCCH type (ZGPAT), P2X purinergic receptor 7 (P2RX7), oxytocin receptor, non-coding RNA (ncRNA), long non-coding RNA (lncRNA), human Human leukocyte antigen (HLA), platelet-derived growth factor (PDGF) receptor (PDGFR) B (PD GFR-B), tissue inhibitor of metalloproteinase 1 (TIMP-1), TI MP-2, IL-23, activin A, intercellular adhesion molecule (ICAM-2), osteopontin Opthalin (OPN), insulin, insulin growth factor binding protein 4 (IGF-BP4) , tumor necrosis factor (TNF) receptor 1 (TNF-R1), ectodysplasin A2 receptor ( XEDAR), and / or one or more genes encoding follistatin The method of claim 1 , comprising one or more SNPs.

11. The SNP is IL-18 SNP rs1946518 and / or rs1872 38. The method of claim 10,

12. The SNPs are ncRNA SNPs Rs11669309, Rs2298075, and and / or Rs10237038.

13. The SNPs are androgen receptor SNPs Rs6152, Rs2223841, and and / or Rs2497938.

14. The SNPs are oxytocin receptor SNPs Rs237887 and Rs2268491; The method according to claim 10, comprising Rs 2,254,298 and / or Rs 7,632,287. Law.

15. The SNP is P2RX7 SNP Rs17525809, Rs28360447, Rs7958311, Rs1718119, Rs2230912, Rs28360457 , Rs2230911, and / or Rs1653624. method.

16. The SNP is lncRNA SNP Rs8028149, Rs16868911, Rs11543230, Rs9309325, Rs12951337, Rs154282 65, Rs 12,683,158, and / or Rs 6,982,502. The method described.

17. 11. The method of claim 10, wherein the SNP comprises HLA gene SNP Rs2269706. method.

18. The SNP is PAX1 / FOXA2 SNP Rs1160312 and / or R 11. The method of claim 10, comprising S6047844.

19. The SNP is HDAC9 SNP Rs2073963 and / or Rs2180 11. The method of claim 10, comprising:

20. 11. The method of claim 10, wherein the SNP comprises HDAC4 SNP Rs9287638. method.

21. The method according to claim 10, wherein the SNP comprises the TARDBP SNP Rs12565727. Method of posting.

22. 11. The method of claim 10, wherein the SNP comprises the AUTS2 SNP Rs6945541. method.

23. 10. The method of claim 10, wherein the SNP comprises the 17q21.31 SNP Rs12373124. The method described above.

24. The method according to claim 10, wherein the SNP comprises SETBP1 SNP Rs10502861. Method of posting.

25. The SNP comprises TNFRSF6B / ZGPAT SNP Rs6010620; The method of claim 10.

26. Mesenchymal Stem Cells for Use in Treating a Disease or Disorder in an End-User Subject A therapeutic composition comprising stem cells and exosomes, a) a composition base; b) The same hair type, hair color, skin type, skin color, race, and / or skin type as the end user. or ethnicity, but the donor never has a disease that is afflicted by said end user subject. Prior to having a single nucleotide polymorphism (SNP) profile indicative of the absence of a disease or disorder and a mesenchymal stem cell and exosome preparation derived from the donor, The exosome preparations were cultured in cells or cell-conditioned media under normal hyperoxic culture conditions. and cells cultured under harsh wound healing conditions. A mesenchymal stem cell and exosome therapeutic composition comprising one member.

27. The SNP is an interleukin 18 (IL-18), an androgen receptor (AR), Histone deacetylase (HDAC)-4 (HDAC4), HDAC9, paired bock PAX1, forkhead box A2 (FOXA2), TAR DNA binding protein protein (TARDBP), autism susceptibility gene 2 (AUTS2), SET-binding protein SETBP1, 17q21.31, tumor necrosis factor receptor superfamily member Bar 6B (TNFRSF6B), zincfin with G-patch domain-containing protein ZGAR CCCH type (ZGPAT), P2X purinergic receptor 7 (P2RX7), oxytocin receptor, non-coding RNA (ncRNA), long non-coding RNA (lncRNA), human Human leukocyte antigen (HLA), platelet-derived growth factor (PDGF) receptor (PDGFR) B (PD GFR-B), tissue inhibitor of metalloproteinase 1 (TIMP-1), TI MP-2, IL-23, activin A, intercellular adhesion molecule (ICAM-2), osteopontin Opthalin (OPN), insulin, insulin growth factor binding protein 4 (IGF-BP4) , tumor necrosis factor (TNF) receptor 1 (TNF-R1), ectodysplasin A2 receptor ( XEDAR), and / or one or more genes encoding follistatin 27. The mesenchymal stem cell and exosome therapeutic composition of claim 26, comprising one or more SNPs. thing.

28. The SNP is IL-18 SNP rs1946518 and / or rs1872 38. The mesenchymal stem cell and exosome therapeutic composition of claim 27.

29. The SNPs are ncRNA SNPs Rs11669309, Rs2298075, and The mesenchymal stem cells and exocrine glands according to claim 27, comprising Rs10237038 and / or Rs10237038. Sosomal therapeutic composition.

30. The SNPs are androgen receptor SNPs Rs6152, Rs2223841, and The mesenchymal stem cells and exosomal cells according to claim 27, comprising Rs2497938 and / or Rs2497938. Therapeutic compositions.

31. The SNPs are oxytocin receptor SNPs Rs237887 and Rs2268491; 28. The method according to claim 27, comprising Rs 2,254,298 and / or Rs 7,632,287. Mesenchymal stem cell and exosome therapeutic composition.

32. The SNP is P2RX7 SNP Rs17525809, Rs28360447, Rs7958311, Rs1718119, Rs2230912, Rs28360457 , Rs2230911, and / or Rs1653624. Mesenchymal stem cell and exosome therapeutic compositions.

33. The SNP is lncRNA SNP Rs8028149, Rs16868911, Rs11543230, Rs9309325, Rs12951337, Rs154282 65, Rs 12683158, and / or Rs 6982502. The described mesenchymal stem cell and exosome therapeutic composition.

34. 28. The method of claim 27, wherein the SNP comprises HLA gene SNP Rs2269706. Mesenchymal stem cell and exosome therapeutic compositions.

35. The SNP is PAX1 / FOXA2 SNP Rs1160312 and / or R 28. The mesenchymal stem cell and exosome therapeutic composition of claim 27, comprising s6047844. thing.

36. The SNP is HDAC9 SNP Rs2073963 and / or Rs2180 439. The mesenchymal stem cell and exosome therapeutic composition of claim 27.

37. 28. The method of claim 27, wherein the SNP comprises HDAC4 SNP Rs9287638. Mesenchymal stem cell and exosome therapeutic compositions.

38. 28. The method of claim 27, wherein the SNP comprises the TARDBP SNP Rs12565727. The mesenchymal stem cell and exosome therapeutic composition described above.

39. 28. The method of claim 27, wherein the SNP comprises the AUTS2 SNP Rs6945541. Mesenchymal stem cell and exosome therapeutic compositions.

40. 27. The method of claim 26, wherein the SNP comprises the 17q21.31 SNP Rs12373124. The mesenchymal stem cell and exosome therapeutic composition described in claim 1.

41. 28. The method according to claim 27, wherein the SNP comprises SETBP1 SNP Rs10502861. The mesenchymal stem cell and exosome therapeutic composition described above.

42. The SNP comprises TNFRSF6B / ZGPAT SNP Rs6010620; The mesenchymal stem cell and exosome therapeutic composition of claim 27.

43. A sac of mesenchymal stem cells and an exosome therapeutic composition according to any one of claims 26 to 42. and administering to a subject any of the above-mentioned compounds to treat, inhibit, reduce, ameliorate, or prevent a disease or disorder. Methods of prevention and / or reversal.

44. The disease or disorder is alopecia, atopic dermatitis, autism spectrum disorder, multiple myelopathy, Sclerosis, chronic pain, depression, anxiety, bipolar disorder, osteoporosis, rheumatoid arthritis, celiac disease , type II diabetes, coronary heart disease, hypertension, multiple coexisting diseases, and / or cancer; 44. The method of claim 43.

45. The alopecia is male pattern baldness, androgenetic alopecia, alopecia areata, cicatricial alopecia, 45. The method of claim 44, comprising terminal alopecia, or female pattern hair loss.

46. The single nucleotide polymorphism (SNP) associated with the disease or disorder in the subject. However, the SNPs Rs6152, Rs2223841, Rs2497938, and Rs116 0312, 6047844, Rs2180439, Rs2073963, Rs12565 727, Rs9287638, Rs6945541, Rs12373124, Rs105 02861, Rs187238, and / or Rs1946518 46. ​​The method of claim 45, comprising:

47. 45. The method of claim 44, wherein the cancer comprises pancreatic cancer or breast cancer.

48. the disease is breast cancer, and the SNP associated with breast cancer in the subject is 48. The method of claim 47, comprising Rs2298075.

49. the disease is pancreatic cancer, and the SNP associated with the pancreatic cancer in the subject is 48. The method of claim 47 comprising NP Rs10237038.

50. The disease or disorder includes an autism spectrum disorder, and the autism spectrum disorder The SNPs associated with 254298, and / or Rs7632287. The method described above.

51. The disease or disorder includes osteoporosis, and the SNP associated with osteoporosis is SNP Rs28360447, Rs28360457, Rs1718119, Rs22 30911, and / or Rs1653624. The method described.

52. the disease or disorder comprises rheumatoid arthritis, and the SNP associated with the rheumatoid arthritis is 45. The method of claim 44, comprising the SNP Rs2269706.

53. the disease or disorder comprises multiple sclerosis, and the SNP associated with multiple sclerosis is One or more of the SNPs Rs17525809 and / or Rs28360447 45. The method of claim 44, comprising the above.

54. the disease or disorder comprises chronic pain, and the SNP associated with the chronic pain is P Rs28360447 and / or Rs7958311, 45. The method of claim 44.

55. The disease or disorder includes atopic dermatitis, and the disease or disorder associated with atopic dermatitis is 45. The method of claim 44, wherein the SNP comprises SNP Rs6010620.

56. the disease or disorder includes hypertension, and the SNP associated with hypertension is 45. The method of claim 44, comprising Rs11669309.

57. the disease or disorder comprises coronary heart disease, and the SNP associated with the heart disease is 45. The method of claim 44, comprising SNP Rs6982502.

58. the disease or disorder comprises type II diabetes, and the SNP associated with type II diabetes is 45. The method of claim 44, comprising the SNP Rs12683158.

59. the disease or disorder comprises celiac disease, and the SNP associated with the celiac disease is 45. The method of claim 44, comprising the SNP Rs15428265.

60. The disease or disorder anxiety and the SNP associated with the anxiety are SNP Rs1 718119. The method of claim 44,

61. the disease or disorder comprises bipolar disorder, and the SNP associated with the bipolar disorder is 45. The method of claim 44, comprising SNP Rs2230912.

62. the disease or disorder includes depression, and the SNP associated with depression is 45. The method of claim 44, comprising Rs8028149.

63. The disease or disorder is characterized in that the SNPs Rs16868911, Rs11543230, R s9309325, and / or Rs12951337, 45. The method according to claim 44.

Images