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WO2021251616A1 - Composition comprenant des exosomes dérivés de cellules souches mésenchymateuses félines et méthode de traitement de maladies inflammatoires à l'aide de celle-ci - Google Patents

Composition comprenant des exosomes dérivés de cellules souches mésenchymateuses félines et méthode de traitement de maladies inflammatoires à l'aide de celle-ci Download PDF

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Publication number
WO2021251616A1
WO2021251616A1 PCT/KR2021/005093 KR2021005093W WO2021251616A1 WO 2021251616 A1 WO2021251616 A1 WO 2021251616A1 KR 2021005093 W KR2021005093 W KR 2021005093W WO 2021251616 A1 WO2021251616 A1 WO 2021251616A1
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exosomes
feline
derived
mesenchymal stem
stem cells
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Korean (ko)
Inventor
서민수
강경구
성수은
최주희
이시준
김길수
윤성호
권영삼
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Daegu Gyeongbuk Medical Innovation Foundation
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/20—Animal feeding-stuffs from material of animal origin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/142—Amino acids; Derivatives thereof
    • A23K20/147—Polymeric derivatives, e.g. peptides or proteins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2066—IL-10
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to a composition for preventing, treating or improving inflammatory diseases, including exosomes derived from mesenchymal stem cells (MSC) of felines, and a method for treating inflammatory diseases in felines using the same.
  • MSC mesenchymal stem cells
  • Inflammation is one of the defense mechanisms of living tissue against tissue damage, external stimuli, or various infectious agents. It is an immune response that occurs locally to restore the damaged area to its original state. That is, the inflammatory response is necessary to protect the living body and remove the products generated by tissue damage. However, when such an inflammatory reaction occurs over a certain level or occurs chronically, it progresses to a disease state such as chronic inflammation, resulting in serious abnormalities.
  • MSC mesenchymal stem cells
  • Another object of the present invention is to provide a feed composition for preventing or improving inflammatory diseases, including exosomes derived from mesenchymal stem cells (MSC) of felines.
  • MSC mesenchymal stem cells
  • Another object of the present invention is to provide a method for treating inflammatory diseases in felines, comprising administering exosomes derived from mesenchymal stem cells (MSC) of felines to felines.
  • MSC mesenchymal stem cells
  • the present invention provides a pharmaceutical composition for preventing or treating inflammatory diseases, including exosomes derived from mesenchymal stem cells (MSC) of felines.
  • MSC mesenchymal stem cells
  • the present invention provides a feed composition for preventing or improving inflammatory diseases, including exosomes derived from mesenchymal stem cells (MSC) of feline animals.
  • MSC mesenchymal stem cells
  • the present invention provides a method for treating inflammatory diseases in felines, comprising administering exosomes derived from mesenchymal stem cells (MSC) of felines to felines.
  • MSC mesenchymal stem cells
  • the present invention provides the use of exosomes derived from mesenchymal stem cells (MSC) of felines for treating inflammatory diseases in felines.
  • MSC mesenchymal stem cells
  • the mesenchymal stem cells may be derived from adipose tissue.
  • the feline animal may be a cat.
  • the exosome may include IL-10 (interleukin-10).
  • the exosomes when the exosomes are treated with macrophages, the expression of pro-inflammatory factors is reduced and the expression of anti-inflammatory factors is increased, so the exosomes derived from mesenchymal stem cells derived from cat adipose tissue are useful for treating inflammatory diseases can be
  • 1A is a microscopic view of culturing cat skin epithelial cells (feline fibroblast cells, fe-fibroblasts) and cat adipose adult stem cells (feline adipose tissue mesenchymal stem cells, fe-AD-MSC).
  • Figure 1b is a graph showing the results of analysis of stem cell markers through flow cytometry analysis of cat AD-MSC.
  • Figures 2a to c confirm the characteristics of the cat AD-MSC and fibroblast exosomes
  • Figure 2a shows the results of observing the cat skin epithelial cell exosomes and the cat fat adult stem cell exosomes under an electron microscope
  • Figure 2b is Exosome surface markers CD9 and CD81 expression intensity is the experimental result by flow cytometry
  • Figure 2c is the exosome particle number and size distribution evaluation results through NTA analysis.
  • Figure 3 compares cytokine and chemokine expression levels between feline fibroblasts and feline AD-MSC exosomes (y-axis represents fluorescence intensity. *p-value ⁇ 0.05, ** ⁇ 0.0001).
  • Figure 4b shows the analysis results of cytokines TNF- ⁇ , IL-1 ⁇ , IL-10 secreted from THP-1 macrophage (*p-value ⁇ 0.05).
  • the present invention provides a pharmaceutical composition for preventing or treating inflammatory diseases, including exosomes derived from mesenchymal stem cells (MSC) of feline animals.
  • MSC mesenchymal stem cells
  • the feline is a family of carnivorous mammals, and includes large animals such as tigers, lions, leopards, and jaguars, the leopard subfamily and the cheetahaceae, and smaller cats including the puma, lynx, bobcat, ocelot, wild cat and domestic cat. It is a concept including a subfamily, and in the present invention, the feline animal may preferably be a cat.
  • exosomes is a cell-derived vesicle that exists in eukaryotes, and is released from cells when multivesicular bodies (MVBs) fuse with the plasma membrane or are directly released from the plasma membrane. do.
  • MVBs multivesicular bodies
  • mesenchymal stem cells refers to stem cells present in cartilage, bone tissue, adipose tissue, and bone marrow stroma differentiated from mesoderm generated by division of a fertilized egg.
  • the mesenchymal stem cells are not particularly limited, but may preferably be adipose-derived mesenchymal stem cells.
  • the adipose-derived stem cells may be stem cells derived from adipose tissue of a mammal, preferably stem cells derived from adipose tissue of a feline animal.
  • the adipose-derived stem cells may be a kind of adult stem cells isolated from adipose tissue. Acquisition of adipose tissue can be obtained incidentally in the conventionally performed liposuction process, so it has the advantage of easily obtaining and culturing a sufficient amount of stem cells, and can secure superior safety compared to bone marrow harvesting.
  • inflammatory disease refers to a disease caused by a chain bioreaction caused by a direct reaction of a humoral mediator constituting the immune system or stimulation of a local or systemic effector system.
  • prevention refers to any action that suppresses or delays the onset of an inflammatory disease by administration of the pharmaceutical composition according to the present invention.
  • treatment refers to any action in which symptoms due to an inflammatory disease are improved or beneficially changed by administration of the pharmaceutical composition according to the present invention.
  • the pharmaceutical composition according to the present invention includes exosomes derived from mesenchymal stem cells (MSC) of felines as an active ingredient, and may include a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carrier is commonly used in formulation, and includes, but is not limited to, saline, sterile water, Ringer's solution, buffered saline, cyclodextrin, dextrose solution, maltodextrin solution, glycerol, ethanol, liposome, and the like. It does not, and may further include other conventional additives, such as antioxidants and buffers, if necessary.
  • diluents, dispersants, surfactants, binders, lubricants and the like may be additionally added to form an injectable formulation such as an aqueous solution, suspension, emulsion, etc., pills, capsules, granules, or tablets.
  • suitable pharmaceutically acceptable carriers and formulations formulations can be preferably made according to each component using the method disclosed in Remington's literature.
  • the pharmaceutical composition of the present invention is not particularly limited in formulation, but may be formulated as an injection or oral ingestion.
  • the pharmaceutical composition of the present invention may be administered orally or administered parenterally (eg, intravenously or subcutaneously) according to a desired method, and the dosage may vary depending on the individual's condition and weight, degree of disease, drug form, although it varies depending on the route and time of administration, it may be appropriately selected by those skilled in the art.
  • composition according to the present invention is administered in a pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type of disease, severity, drug activity, drug Sensitivity to, administration time, administration route and excretion rate, duration of treatment, factors including concomitant drugs, and other factors well known in the medical and veterinary fields.
  • the composition according to the present invention may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple. In consideration of all of the above factors, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, which can be easily determined by those skilled in the art.
  • the effective amount of the composition according to the present invention may vary depending on the age, sex, and weight of the individual, and may be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, and the like.
  • the exosome may include IL-10.
  • the IL-10 is an anti-inflammatory cytokine that down-regulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules in macrophages, can block NF- ⁇ B activity, and regulate the JAK-STAT signaling pathway. get involved in Therefore, when the subject is treated with IL-10, it exhibits an anti-inflammatory effect.
  • the present invention provides a feed composition for preventing or improving inflammatory diseases, comprising exosomes derived from mesenchymal stem cells (MSC) of felines.
  • MSC mesenchymal stem cells
  • the term “improvement” refers to any action that at least reduces a parameter related to the condition being treated, for example, the severity of symptoms.
  • the feed composition may be used in the form of feed or feed additive.
  • the feed additives include organic acids such as citric acid, humic acid, adipic acid, lactic acid, and malic acid, or phosphates such as sodium phosphate, potassium phosphate, acid pyrophosphate, polyphosphate (polyphosphate), polyphenol, catechin, alpha-tocopherol, rosemary Extract, vitamin C, green tea extract, licorice extract, chitosan, tannic acid, any one or more of natural antioxidants such as phytic acid may be further included.
  • the composition When used as a feed, the composition may be formulated in a conventional feed form, and may include common feed ingredients together.
  • the feed additive and feed include grains such as milled or crushed wheat, oats, barley, corn and rice; plant protein feeds, such as feeds based on rape, soybean, and sunflower; animal protein feeds such as blood meal, meat meal, bone meal and fish meal; Sugar and dairy products, for example, may further include dry ingredients made of various powdered milk and whey powder, and may further include nutritional supplements, digestion and absorption enhancers, growth promoters, etc.
  • the feed additive may be administered to the animal alone or in combination with other feed additives in an edible carrier.
  • the feed additives can be easily administered to the animal as a top dressing, directly mixing them into the animal feed, or in an oral formulation separate from the feed.
  • a pharmaceutically acceptable edible carrier as well known in the art to prepare an immediate release or sustained release formulation.
  • Such edible carriers may be solid or liquid, for example corn starch, lactose, sucrose, soy flakes, peanut oil, olive oil, sesame oil and propylene glycol.
  • the feed additive may be a tablet, capsule, powder, troche or sugar-containing tablet or top dressing in microdispersed form.
  • the feed additive may be in the form of a gelatin soft capsule, or a syrup or suspension, emulsion, or solution.
  • the feed may comprise any protein-containing organic flour conventionally used to meet the dietary needs of animals.
  • protein-containing flours typically consist primarily of corn, soy flour, or corn/soy flour mix.
  • the feed additives and feed may contain adjuvants, for example, preservatives, stabilizers, wetting or emulsifying agents, solution accelerators, and the like.
  • the feed additive may be used by being added to animal feed by penetrating, spraying, or mixing.
  • the feed or feed additive of the present invention can be applied to the diet of many animals including mammals, preferably a feline animal, and more preferably a cat.
  • the present invention provides a method for treating inflammatory diseases in felines, comprising administering to the feline mesenchymal stem cell (MSC)-derived exosomes.
  • MSC feline mesenchymal stem cell
  • the present invention provides the use of exosomes derived from mesenchymal stem cells (MSC) of felines for treating inflammatory diseases in felines.
  • MSC mesenchymal stem cells
  • exosomes When feline exosomes are administered to felines, exosomes fuse with the plasma membrane of cells and release internal substances due to the general nature of exosomes.
  • compositions, therapeutic use, and treatment method may be equally applied as long as they do not contradict each other.
  • Feline fibroblasts and feline adipose tissue-derived mesenchymal stem cells were used, respectively, derived from feline skin tissue and abdominal adipose tissue.
  • fAD-MSC was provided by laboratory animal resources bank (LAREB, Ministry of Food and Drug Safety of Korea).
  • Cat's skin and adipose tissue were isolated, then rinsed with 70% EtOH and cold PBS, and then digested using 0.45 ⁇ m filter-filtered collagenase type I 2 mg/mL (gibco) in a 37 °C incubator for 30 min. made it Then, the digested solution was added to a 70 ⁇ m strainer, and the filtered solution was centrifuged at 3000 x g for 5 minutes.
  • Feline fibroblasts and feline AD-MSC were prepared from 10% exosome-depleted FBS (gibco), 1% penicillin/streptomycin (gibco), 10ug/mL recombinant human FGF-basic (Peprotech), 10ug/mL recombinant human It was maintained in low glucose-DMEM (gibco) supplemented with PDGF-BB (Peprotech) and 25 ug/mL plasmosin (InvivoGen) for mycoplasma prophylaxis. All cells were cultured at 37° C. and 5% CO 2 incubator conditions.
  • Example 1-2 Isolation of fAD-MSC exosomes.
  • fAD-MSCs were incubated for 48 hours in 175T-flasks and then harvested. Exosomes were purified from the cell culture medium and cells were removed by centrifugation at 300 x g for 10 min. The supernatant was centrifuged again at 2500 x g for 25 min to remove cell debris, apoptotic bodies. Then, the supernatant was ultracentrifuged at 100,000 ⁇ g for 120 minutes using a type 90Ti rotor (Beckman Coulter). A pellet appeared at the bottom of the ultracentrifuge tube, the supernatant was discarded and the pellet resuspended in 200 ml of PBS filtered with a 0.22 ⁇ m filter. Exosomal protein concentration was measured by the PierceTM BCA assay kit (Thermo Fisher Scientific 23225).
  • fAD-MSCs were visualized under a bright field microscope, and then flow cytometry was performed to identify cell surface markers.
  • Flow cytometry analysis was performed with flow cytometry Galios (Beckman Coulter).
  • CD105 Bio-Rad, MCA1557
  • CD90 BioLegend, 555596
  • CD44 BioLegend, 103024
  • CD45 BioLegend, 555482
  • CD34 BioLegend, 343504
  • CD14 Bio Cells were stained with an antibody such as -Rad, MCA1568).
  • Antibodies were conjugated with FITC or PE fluorescent dyes, and for the analysis of exosomes, 200 ⁇ L of isolated exosomes were mixed with 10 ⁇ L of aldehyde/sulfate-latex beads 4% w/v (ThermoFishcer Scientific) at room temperature 15 Incubate for min and add 1 mL volume of PBS (supplemented with 0.1% BSA) to the exosome/bead mixture.
  • Exosomes isolated from feAD-MSCs and fe-fibroblasts were resuspended in cold distilled water.
  • the exosome suspension was loaded onto a formvar carbon coated grid (Ted Pella Inc.) and fixed in 2% paraformaldehyde for 10 minutes, then the solution was removed and the sample was dried.
  • the grid was observed by bioTEM (Hitachi HT7700).
  • Nanoparticles tracking analysis was performed with a PMX120 (Particle Metrix) instrument according to the manufacturer's manual.
  • fAD-MSC and fe-Fibroblasts exosome solutions were quantified using the Quantibody® feline cytokine array kit (RayBiotech, QAF-CYT-1). Exosomal proteins were diluted to 250 ⁇ g/mL for each array and loaded with a total sample volume of 100 ⁇ l and performed according to the manufacturer's protocol. Signals were measured by an Innopsys Innoscan laser scanner with Cy3 wavelength. Analysis results were quantified with Mapix version 7.2.0.
  • Example 1-7 Treatment of THP-1 cells with LPS and exosomes
  • the isolated cat AD-MSC was attached to a plastic culture dish with typical MSC characteristics, and it was confirmed that the morphology had a spindle shape like a fibroblast ( FIG. 1A ).
  • Feline AD-MSCs confirmed the positive expression of CD105, CD90, and CD44 and negative expression of CD14, CD34, and CD45 on the cell surface through flow cytometry (Fig. 1b). These results suggest that isolated feline AD-MSCs have the general characteristics of MSCs.
  • Serum-free or xeno-free media for cell culture contain many albumin and other proteins. Since serum albumin and exosomes contained in FBS affect the purity of the isolated exosomes, the present invention uses FBS from which the exosomes have been removed, and to confirm the purified exosomes, TEM, FACS and NTA analysis were performed. carried out.
  • the isolated exosomes showed a general exosome shape, and the size was 100-200 nm in diameter and spherical. It was confirmed that the dark and thick exosome membrane had a lipid bilayer membrane through the TEM image (FIG. 2a).
  • Exosomes made of multivesicular bodies have several biomarkers such as tetraspanin, fusion protein and MVB biogenesis marker. Among them, since tetraspanins are expressed in the exosome membrane, tetraspanins such as CD9 and CD81 were detected using flow cytometry. Since flow cytometry is usually performed on cells, but exosomes are much smaller than cells, aldehyde/latex beads with a diameter of about 4 ⁇ m were used for flow cytometry. Positive expression of over 90% of CD9 and CD81 was detected in exosomes through flow cytometry (FIG. 2b).
  • the cat fibroblast-derived exosomes had an average diameter of 156.4 nm and a concentration of 2.3x10 10 particles/mL, and the cat AD-MSC-derived exosomes had an average diameter of 155.4 nm and a concentration of 1.2x10 10 particles/mL (Fig. 2c) .
  • Cytokine and chemokine levels were compared between exosomes derived from feline AD-MSC and exosomes derived from feline fibroblasts.
  • experiments were performed by adjusting the protein concentration to 250 ⁇ g/mL, the concentration recommended in the cytokine array manual.
  • pro-inflammatory factors such as IL-2, IFN- ⁇ , IL-1 ⁇ , IL-8 and RANTES were expressed at low levels in exosomes derived from cat AD-MSC.
  • IL-10 an anti-inflammatory factor, was significantly increased in feline AD-MSC-derived exosomes (FIG. 3).
  • fAD-MSC-derived exosomes reduce the inflammatory response through high levels of the anti-inflammatory factor, IL-10.
  • exosomes derived from feline fibroblasts and cat AD-MSC were used, respectively. processed and analyzed.
  • TNF- ⁇ the pro-inflammatory factor
  • the pro-inflammatory factor, TNF- ⁇ increases.
  • TNF- ⁇ was found to be an average of 5.8 pg/mL, and when treated with LPS, it was significantly increased to an average of 336.7959 pg/mL.
  • feline fibroblast exosomes were treated at the same time as LPS was treated, the average TNF- ⁇ was 373.0363 pg/mL, which was similar to that when treated with LPS alone.
  • LPS and feline AD-MSC axosomes were simultaneously treated, the average was reduced to 186.7481 pg/ml.
  • TNF-alpha expression level of the cat fibroblast exosome and the cat AD-MSC exosome was compared, it was confirmed that TNF- ⁇ was significantly reduced when the cat AD-MSC exosome was treated.
  • IL-1 ⁇ Another pro-inflammatory factor, IL-1 ⁇ , was not secreted from untreated macrophages, and was significantly increased to 669.4461 pg/mL when LPS was treated.
  • LPS and feline fibroblast exosomes were treated, the average IL-1 ⁇ was 774.032 pg/mL, which was similar to that of LPS alone.
  • LPS and cat AD-MSC exosomes were treated, the average was 536.4394 pg/mL, and it was confirmed that IL-1beta was significantly reduced compared to when treated with cat fibroblast exosomes.
  • IL-10 known as an anti-inflammatory factor
  • IL-10 was expressed as 0 in macrophages that were not treated with anything, and was expressed as much as 183.3961 pg/mL when treated with LPS.
  • feline fibroblast exosomes were treated simultaneously with LPS, the average level was lowered to 159.552 pg/mL.
  • the average expression level of IL-10 was 230.00 pg/mL, and it was confirmed that the anti-inflammatory factor IL-10 increased after treatment with cat AD-MSC-derived exosomes.
  • IL-10 which is known as an anti-inflammatory factor
  • the exosomes when the exosomes are treated with macrophages, the expression of pro-inflammatory factors is reduced and the expression of anti-inflammatory factors is increased, so the exosomes derived from mesenchymal stem cells derived from cat adipose tissue are useful for treating inflammatory diseases can be

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Abstract

La présente invention se rapporte à une composition permettant de prévenir, de traiter ou de soulager des maladies inflammatoires, qui comprend des exosomes dérivés de cellules souches mésenchymateuses félines ; et à une méthode de traitement de maladies inflammatoires chez un félin en utilisant la composition. La présente invention a découvert que l'expression d'un facteur anti-inflammatoire IL-10 est plus élevée dans des exosomes dérivés de cellules souches mésenchymateuses dérivées du tissu adipeux que dans des exosomes dérivés de fibroblastes, et, lorsque les exosomes sont utilisés pour traiter des macrophages, l'expression de facteurs pro-inflammatoires diminue tandis que l'expression de facteurs anti-inflammatoires augmente. Ainsi, les exosomes dérivés de cellules souches mésenchymateuses félines dérivées du tissu adipeux peuvent être avantageusement utilisés pour le traitement de maladies inflammatoires.
PCT/KR2021/005093 2020-06-10 2021-04-22 Composition comprenant des exosomes dérivés de cellules souches mésenchymateuses félines et méthode de traitement de maladies inflammatoires à l'aide de celle-ci Ceased WO2021251616A1 (fr)

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US20150190429A1 (en) * 2012-07-18 2015-07-09 Universitaet Duisburg-Essen Use of Preparations Comprising Exosomes Derived From Mesenchymal Stem Cells (MSCs) in the Prevention and Therapy of Inflammatory Conditions
JP2018531979A (ja) * 2015-11-02 2018-11-01 タイジェニックス、ソシエダッド、アノニマ、ウニペルソナルＴｉｇｅｎｉｘ Ｓ．Ａ．Ｕ． 間葉幹細胞由来のエクソソームおよびその使用
KR101776886B1 (ko) * 2016-11-18 2017-09-08 가톨릭대학교 산학협력단 면역 조절능이 향상된 중간엽 줄기세포 및 이의 용도
US20200163998A1 (en) * 2017-07-17 2020-05-28 Codiak Biosciences, Inc. Nanovesicles produced from mesenchymal stromal cells for anti-inflammatory applications
WO2019099927A1 (fr) * 2017-11-16 2019-05-23 Board Of Regents, The University Of Texas System Procédés de production d'exosomes dérivés de csm

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