WO2020015264A1 - Cellule souche dentaire et utilisation de cette dernière - Google Patents

Cellule souche dentaire et utilisation de cette dernière Download PDF

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WO2020015264A1
WO2020015264A1 PCT/CN2018/116834 CN2018116834W WO2020015264A1 WO 2020015264 A1 WO2020015264 A1 WO 2020015264A1 CN 2018116834 W CN2018116834 W CN 2018116834W WO 2020015264 A1 WO2020015264 A1 WO 2020015264A1
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stem cells
dental
dental pulp
psoriasis
group
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PCT/CN2018/116834
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English (en)
Chinese (zh)
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孟虹芳
王�华
吴祖泽
唐仲雄
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北京三有利和泽生物科技有限公司
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Publication of WO2020015264A1 publication Critical patent/WO2020015264A1/fr

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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
    • A61K35/14—Blood; Artificial blood
    • 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
    • A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material

Definitions

  • the invention relates to the application of stem cells and genetically modified stem cells in the treatment of psoriasis of unknown etiology and related diseases, in particular, dental-derived stem cells (such as dental pulp stem cells (DPSC) and HGF gene-modified teeth).
  • dental-derived stem cells such as dental pulp stem cells (DPSC) and HGF gene-modified teeth.
  • DPSC dental pulp stem cells
  • HGF gene-modified teeth Use of source stem cells in the treatment of psoriasis and related diseases.
  • the invention relates to a stem cell, a genetically modified stem cell, particularly a dental-derived stem cell, a genetically modified dental-derived stem cell, and a composition or a composition comprising the stem cell and / or the genetically-modified stem cell, particularly a dental-derived stem cell, a genetically modified dental-derived stem cell, or Kit.
  • the main symptoms of psoriasis are itching of the skin, which may have exudates or bleeding points; thickening of the skin, scales, and erythema; excessive proliferation of keratinocytes, the generation of new blood vessels, the infiltration of inflammatory cells, the Rise and so on.
  • Some patients have low cellular immune function; some have increased serum IgG, IgA, and IgE; some patients have anti-IgG antibodies in their serum; some have detected anti-keratin autoantibodies in the epidermal stratum corneum using immunofluorescence technology.
  • the current treatments for psoriasis include traditional Chinese medicine, western medicine and biological therapy.
  • Traditional Chinese medicine methods include: Chinese medicine application, fumigation, oral administration, acupuncture, cupping, etc.
  • Western medicine treatments include: external medicines, such as topical keratin promoters, glucocorticoids, vitamin D3 derivatives, vitamin A acid cream, cytokine antagonists, etc .; internal medicines, such as cyclosporine, vitamin A acid, methylamine Pterin, etc .; biological therapies are currently mainly inflammatory factor antagonists, such as Enli, Likek, Xiu Merole and so on. There are also other treatments such as autohemotherapy, light therapy and so on.
  • Stem cells can proliferate and differentiate, can homing, colonize, repair, and regenerate tissues after transplantation, and do not have the toxicity and tolerance problems of the above-mentioned therapy. Therefore, the application of stem cells has the function of multiplying and differentiating, especially in the process of tissue damage for unknown reasons, the unknown link in the middle may prevent, repair, and regenerate to achieve the purpose of treatment. This has been confirmed by the unexpected effects of stem cells on some diseases. For this reason, the inventors tried to use dental-derived stem cells to treat psoriasis with a view to achieving a certain effect.
  • HGF-DPSC HGF-modified dental-derived stem cells
  • stem cells such as dental stem cells, especially dental pulp stem cells
  • HGF hepatocyte growth factor
  • a first aspect of the invention relates to the use of stem cells in the manufacture of a product for the treatment of psoriasis-related diseases.
  • the stem cells are preferably dental stem cells, more preferably genetically modified dental stem cells, and are preferably selected from dental pulp stem cells, deciduous dental pulp stem cells, periodontal ligament stem cells and root canine teeth.
  • One or more of the nipple stem cells are preferably dental stem cells, more preferably genetically modified dental stem cells, and are preferably selected from dental pulp stem cells, deciduous dental pulp stem cells, periodontal ligament stem cells and root canine teeth.
  • One or more of the nipple stem cells are preferably dental stem cells, more preferably genetically modified dental stem cells, and are preferably selected from dental pulp stem cells, deciduous dental pulp stem cells, periodontal ligament stem cells and root canine teeth.
  • a second aspect of the invention relates to the use of genetically modified stem cells in the manufacture of a product for the treatment of psoriasis-related diseases.
  • a second aspect of the present invention relates to genetically modified stem cells, which is characterized in that an exogenous hepatocyte growth factor gene is introduced into the stem cells and the exogenous hepatocyte growth factor is expressed.
  • the dental-derived stem cells are selected from the group consisting of dental pulp stem cells, deciduous dental pulp stem cells, periodontal ligament stem cells, and apical dental papilla stem cells.
  • a dental-derived stem cell introduces an exogenous hepatocyte growth factor gene into a dental-derived stem cell through an adenovirus or an adeno-associated virus vector.
  • the invention also relates to a composition
  • a composition comprising a therapeutically effective amount of the above-mentioned stem cells and optionally a pharmaceutically acceptable carrier or excipient, said composition for reducing inflammatory factors and treating psoriasis-related diseases.
  • the invention also relates to the use of hepatocyte growth factor in the preparation of a product for treating psoriasis-related diseases.
  • the stem cells are preferably dental-derived stem cells selected from one or more of dental pulp stem cells, deciduous dental pulp stem cells, periodontal ligament stem cells, and apical dental papilla stem cells.
  • the dental-derived stem cells are dental pulp stem cells.
  • the genetically modified dental-derived stem cells are hepatocyte growth factor (HGF) gene-modified dental pulp stem cells.
  • HGF hepatocyte growth factor
  • the invention also relates to a composition
  • a composition comprising a therapeutically effective amount of the dental stem cells of any of the first and second aspects of the invention, and optionally a pharmaceutically acceptable carrier or excipient.
  • the invention also relates to a kit comprising a therapeutically effective amount of the dental stem cells of any of the first and second aspects of the invention and optionally a pharmaceutically acceptable carrier or excipient.
  • the composition is a saline suspension of dental pulp stem cells according to the first aspect of the present invention.
  • the composition is a saline suspension of hepatocyte growth factor (HGF) gene-modified dental pulp stem cells according to the second aspect of the present invention.
  • HGF hepatocyte growth factor
  • dental pulp stem cells are firstly separated and cultured from dental pulp, and the obtained dental pulp stem cells are tested for cell surface markers and osteogenic and adipogenic differentiation potentials, and proved to be dental pulp stem cells. Then, the obtained dental pulp stem cells were made into a cell suspension, and experimentally proved that dental pulp stem cells, especially genetically modified dental pulp stem cells, have application in treating psoriasis.
  • the invention therefore also relates to a composition comprising an effective amount of dentally derived stem cells, said composition being useful for the treatment of related diseases such as psoriasis.
  • the present invention confirms that hepatocyte growth factor (HGF) gene-modified dental pulp stem cells have better use in treating psoriasis.
  • HGF hepatocyte growth factor
  • the invention therefore also relates to a composition comprising an effective amount of genetically modified dental-derived stem cells, said composition being useful for the treatment of related diseases such as psoriasis.
  • a second aspect of the present invention relates to a genetically modified tooth-derived stem cell, which is characterized in that an exogenous hepatocyte growth factor gene is introduced into the tooth-derived stem cell and the hepatocyte growth factor is expressed.
  • the expression of hepatocyte growth factor refers to secreted expression secreted outside the cell.
  • the method for introducing an exogenous hepatocyte growth factor gene into a tooth-derived stem cell is a method commonly used in the art for introducing an exogenous gene into a cell, and examples thereof include virus transfection, plasmid transfection, and liposome transfection.
  • the method for introducing a foreign gene into a tooth-derived stem cell is a virus transfection method, for example, an adenovirus or an adeno-associated virus transfection.
  • the virus is an adenovirus.
  • the HGF is human hepatocyte growth factor and its gene sequence (for details, please refer to the record on the human hepatocyte growth factor on the NCBI website: https: //www.ncbi.nlm.nih .gov / nuccore / M29145.1) is described in Miyazawa K, et al., Molecular cloning and sequence analysis of human cDNA for human hepatocyte growth. Biochem Bios Res Commun, 1989, 163 (2): 967-973.
  • the preparation method of HGF-modified dental stem cells is:
  • Isolate and purify dental-derived stem cells such as dental pulp stem cells, deciduous dental pulp stem cells, periodontal ligament stem cells, root tip dental papilla stem cells
  • dental-derived stem cells such as dental pulp stem cells, deciduous dental pulp stem cells, periodontal ligament stem cells, root tip dental papilla stem cells
  • hepatocyte growth factor for example, a recombinant adenovirus (Ad-HGF) carrying a human hepatocyte growth factor gene is used for modification. 24 hours after modification, the cell suspension can be collected for injection treatment.
  • Ad-HGF recombinant adenovirus
  • the genetically modified dental-derived stem cells refer to dental pulp stem cells modified with HGF, that is, dental pulp stem cells that express a large amount of HGF by introducing HGF genes.
  • a method for treating psoriasis using dental-derived stem cells or HGF-modified dental-derived stem cells is:
  • Imiquimod was applied to the back of mice to establish a psoriasis mouse model, and dental pulp stem cells or HGF-modified dental pulp stem cell injections were injected into the tail vein.
  • the treatment effect was evaluated by the indicators of psoriasis skin area and disease severity (PASI) score, pathological section of skin lesion, and concentration of various components in serum.
  • PASI psoriasis skin area and disease severity
  • the present invention successfully verified the therapeutic effect of stem cells such as dental stem cells (especially dental pulp stem cells) on psoriasis of unknown etiology, and provided favorable evidence for expanding the clinical application of dental stem cells; meanwhile, it proved that genes (especially HGF Gene) modified dental-derived stem cells have a more significant therapeutic effect on the disease.
  • the present invention shows that dental-derived stem cells and HGF can be used synergistically for the treatment of psoriasis and related diseases.
  • Figures 1 and 2 show the results of flow-type identification of dental pulp stem cells and umbilical cord stem cell surface markers.
  • Figure 1 Logistic identification of dental pulp stem cell surface markers.
  • Figure 2 Logistic identification of umbilical cord stem cell surface markers.
  • Figures 3 and 4 show the results of osteogenic and adipogenic differentiation of dental pulp stem cells and umbilical cord stem cells.
  • Figure 3 Osteoblastic (left), adipogenic (right) differentiation staining results of dental pulp stem cells.
  • Figure 4 Osteoblastic (left) and adipogenic (right) differentiation staining results of umbilical cord stem cells.
  • Figure 5-9 shows the therapeutic effect of subcutaneous injection of dental pulp stem cells on IMQ-induced psoriasis-like mice.
  • Figure 5 Morphological observation of back skin lesions of mice in each group with days of treatment
  • Figure 6 Trend graph of PASI scores and treatment days of mice in each group
  • Figure 7 Histological observation of skin lesions of mice in each group
  • Figure 8 Results of epidermal thickness measurement on skin lesions of mice in each group
  • Figure 9 Results of determination of serum IL-6 content in mice of each group.
  • Figures 10-12 show the therapeutic effect of intravenous injection of dental pulp stem cells or HGF-modified dental pulp stem cells on IMQ-induced psoriasis-like mice.
  • Figure 10 Histological observation of back skin lesions of mice in each group
  • Figure 11 Determination of the relative expression of IL-17A and IL-22 in the skin lesions of the back of each group of mice;
  • Figure 12 Determination of serum IL-6 and TNF- ⁇ contents of mice in each group
  • 13-17 are the therapeutic effects of intravenous injection of dental pulp stem cells or umbilical cord stem cells on IMQ-induced psoriasis-like mice.
  • Figure 13 Results of skin thickening measurement on the skin lesions on the back of mice in each group
  • Figure 14 Histological observation of skin lesions of mice in each group
  • Figure 15 Determination of the relative expression of IL-17A in the skin lesions of the back of each group of mice;
  • Figure 17 Calculation of spleen index of mice in each group.
  • the tooth is aseptically extracted in the operating room of Beijing Dental Hospital affiliated to Capital Medical University.
  • the aseptic extraction of an impacted third molar or orthodontics under anesthesia requires tooth extraction.
  • Freshly extracted teeth were immediately placed in a centrifuge tube filled with sterile PBS and antibiotics, and dental pulp stem cells were isolated and cultured within 12 hours.
  • the dental pulp tissue was taken from the crown of the extracted tooth, washed repeatedly with PBS, cut as much as possible, placed in a solution containing 3mg / ml type I collagenase and 4mg / ml Dispase, and digested in a water bath at 37 ° C for 0.5-1 hour.
  • Cells were collected on a cell sieve, centrifuged at 1000 rpm for 10 min, and resuspended into a single cell suspension with an appropriate amount of medium.
  • the cells were seeded in a 10 cm petri dish, cultured in an ⁇ -MEM medium (containing 10% fetal bovine serum, 2 mmol / L glutamine) at 37 ° C. and 5% CO 2 , and the solution was changed every 3-5 days. Cell growth was observed daily under an inverted microscope. After 1-2 weeks, cloned cells were removed and passaged with 0.25% trypsin. Obtain dental pulp stem cells.
  • the umbilical cord was stored in a centrifuge tube containing sterile PBS and antibiotics, and the umbilical cord stem cells were isolated and cultured within 12 hours. Take out the umbilical cord in the clean bench, wash it repeatedly with PBS, cut it into about 2cm fragments, and remove the blood vessels (one umbilical vein and two umbilical arteries). Take out the gel-like tissue and cut it into 1mm 3 tissue pieces.
  • Osteogenic differentiation Cells in logarithmic growth phase were seeded into a 24-well cell culture plate at a density of 1 ⁇ 10 4 cells / well, and cultured in an incubator at 37 ° C., 5% CO 2 , and 95% humidity. After 24 hours, osteogenic induction fluid was added, and the fluid was changed every 4 days. Identification was performed with alizarin red staining 3 weeks after induction.
  • Adipogenic differentiation Cells in logarithmic growth phase were seeded in a 24-well cell culture plate at a density of 1.5 ⁇ 10 4 cells / well, and cultured in an incubator at 37 ° C., 5% CO 2 , and 95% humidity. After 24 hours, the adipogenic induction solution was added, and the solution was changed every 4 days. Identification was performed with Oil Red O staining 2 weeks after induction.
  • Test results (see Figures 1 and 2): After dental pulp and umbilical cord stem cells were induced by osteogenesis, alizarin red staining was positive; after adipogenic induction, obvious fat droplets were formed in oil red O stained cells. The above results indicate that the isolated pulp and umbilical cord stem cells have osteogenic and adipogenic differentiation potential.
  • Tooth-derived stem cells were seeded at a density of 1 ⁇ 10 4 cells / cm 2. After 24 hours of culture, Ad-HGF was added at 150 MOI.
  • Ad-HGF was added at 150 MOI.
  • the title is “ A recombinant adenovirus and its application in the treatment of myocardial ischemia "), modifying dental derived stem cells to obtain HGF-modified dental derived stem cells.
  • Example 2 Therapeutic effects of subcutaneous injection of dental pulp stem cells on a mouse model of IMQ-induced psoriasis.
  • mice were purchased, reared for one week, and shaved on the back 1 day before the experiment
  • mice All mice were randomly divided into:
  • Dental pulp stem cell injection group (IMQ + DPSC): dental pulp stem cells (2 ⁇ 10 6 cells) were injected subcutaneously on the first day and the sixth day before applying 5% imiquimod cream, respectively.
  • the area of psoriasis lesions and disease severity (PASI) scores were used to observe the changes of skin lesions in psoriasis-like mouse models.
  • the skin lesions were cut out and HE stained to observe the degree of keratinization and inflammatory cell infiltration.
  • the thickness of epidermal layer of pathological section was measured.
  • mice The venous blood of the mice was collected, and the IL-6 concentration was measured to evaluate the inflammatory response of the mice.
  • the epidermal thickness and inflammatory infiltration of the drug treatment group and the dental pulp stem cell injection group were lighter, but the dermal hyperplasia and inflammation of the drug treatment group were milder. Cell infiltration and other phenomena are still more obvious than those in the dental pulp stem cell injection group, so the treatment effect of the dental pulp stem cell injection group is better than that of the drug treatment group; the results of statistical calculation of the epidermal thickness of the pathological section show that (Figure 8), the dental pulp stem cell injection group The skin thickness of the drug treatment group was significantly lower than that of the model group. The pulp thickness of the dental pulp stem cell injection group was the smallest, and the difference was statistically significant (p ⁇ 0.05).
  • IL-6 is a cytokine with multiple potentials, and may be a growth factor for keratinocytes.
  • the excessive proliferation of psoriatic epidermis may be partly caused by the excessive production of this cytokine.
  • the IL-6 content in the model group, the drug treatment group, and the dental pulp stem cell injection group showed that the expression level of IL-6 in the dental pulp stem cell injection group and the drug treatment group was significantly lower than that in the model group. The difference was statistically significant (p ⁇ 0.05).
  • subcutaneous injection of dental pulp stem cells or application of calcipotriol ointment can slow the occurrence of psoriasis, reduce the symptoms of psoriasis, and accelerate the recovery of psoriasis-like skin lesions.
  • the treatment effect of dental pulp stem cells is more obvious.
  • Example 3 Comparison of the therapeutic effects of tail vein injection of dental pulp stem cells and HGF gene-modified dental pulp stem cells on IMQ-induced psoriasis mouse models.
  • mice were purchased, reared for one week, and shaved on the back 1 day before the experiment
  • mice All mice were randomly divided into:
  • IMQ IMQ-induced tail vein injection of the same amount of saline as the treatment group on day -1, and sacrifice on day 6 for sampling.
  • Treatment group 1 (DPSC). On the first day of IMQ induction, dental pulp stem cell treatment was performed (2 ⁇ 10 6 cells were injected into the tail vein), and samples were sacrificed on day 6.
  • HGF-DPSC HGF-transfected dental pulp stem cell treatment was performed on day -1 of IMQ induction (2 ⁇ 10 6 cells were injected into the tail vein), and samples were sacrificed on day 6.
  • mice The venous blood of mice was collected and the serum inflammatory cytokine concentrations were measured.
  • the treatment group 2 had a stronger inhibitory effect on the increased expression of IL-17A and IL-22 in the model.
  • the results in Figure 12 show that IL-6, TNF- ⁇ is highly expressed in patients with psoriasis, and it can promote keratinogenesis and enhance inflammation.
  • the multifactorial test results of the serum of each group of mice showed that the concentrations of IL-6 and TNF- ⁇ in the model group increased, and the two treatment groups had a decrease in these two factors.
  • the IL-6 The concentration of TNF- ⁇ was significantly lower than that of treatment group 1.
  • dental pulp stem cells or HGF-transfected dental pulp stem cells have a therapeutic effect on imiquimod-induced psoriasis in a mouse model; HGF-transfected dental pulp stem cells have a better therapeutic effect.
  • Example 4 Comparison of the therapeutic effects of tail vein injection of dental pulp stem cells and umbilical cord stem cells on IMQ-induced psoriasis mouse models.
  • mice were purchased, reared for one week, and shaved on the back 1 day before the experiment
  • mice All mice were randomly divided into:
  • IMQ IMQ-induced tail vein injection of the same amount of saline as the treatment group on day -1, and sacrifice on day 6 for sampling.
  • Treatment group 1 dental pulp stem cell treatment was performed on day -1 of IMQ induction (2 ⁇ 10 6 cells were injected into the tail vein), and samples were sacrificed on day 6.
  • mice The venous blood of mice was collected and the serum inflammatory cytokine concentrations were measured.
  • mice were weighed, the spleen was taken, and the spleen index was calculated.
  • Skin thickening is a major symptom of psoriasis.
  • the results of skin thickening data showed (Figure 13) that treatment group 1 and UC group alleviated IMQ-induced psoriasis-like skin thickening, of which treatment group 1 had the smallest skin thickening; pathological sections showed ( Figure 14)
  • the stratum corneum is incomplete, with severe dermal hyperplasia and inflammatory cell infiltration, accompanied by erythrocyte overflow.
  • the treatment group 1 and treatment group 2 have significantly reduced keratinocytes, and the thickness of the epidermis is significantly lower than that in the model group.
  • the results in Figure 16 showed that the IL-17F concentration in patients with psoriasis increased, and the serum of psoriatic mouse model
  • the results of IL-17F concentration showed that DPSC reduced the elevated IL-17F in the serum of the mouse model significantly better than the treatment group 2
  • the results in Figure 17 showed that the spleen of the mouse model of psoriasis induced by IMQ was significantly increased. Large, the spleen index was higher than that of the blank group, and the spleen of the treatment group 1 The number has decreased compared with the model group, the treatment group and the spleen index 2 is even significantly higher than the model group.
  • dental pulp stem cells or umbilical cord stem cells have therapeutic effects on imiquimod-induced psoriasis in a mouse model; dental pulp stem cells have a better therapeutic effect.
  • dental pulp stem cells have a therapeutic effect on the elevated spleen index of model mice, while umbilical cord stem cells not only have no therapeutic effect, but also promote a higher spleen index of model mice.

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Abstract

L'invention concerne une cellule souche et l'utilisation d'une cellule souche génétiquement modifiée. En particulier, l'invention concerne une cellule souche dentaire et l'utilisation d'une cellule souche dentaire génétiquement modifiée dans la préparation d'un produit pour le traitement du psoriasis et de maladies associées. L'invention concerne également une composition ou un kit de réactifs comprenant des cellules souches dentaires et/ou des cellules souches dentaires génétiquement modifiées. Les cellules souches de pulpe dentaire modifiées par le gène HGF sont mieux au traitement du psoriasis que les cellules souches de pulpe dentaire, et le HGF et les cellules souches dentaires peuvent être utilisés en coordination pour le traitement de maladies liées au psoriasis.
PCT/CN2018/116834 2018-07-17 2018-11-22 Cellule souche dentaire et utilisation de cette dernière WO2020015264A1 (fr)

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US20170216362A1 (en) * 2016-01-29 2017-08-03 Tokyo Women's Medical University Cell sheet composition for inhibiting progression of renal disorder, method of producing the same, and method of inhibiting progression of renal disorder using the same

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CN101626772A (zh) * 2007-03-22 2010-01-13 奥西里斯治疗公司 间充质干细胞及其用途
CN103191154A (zh) * 2012-01-06 2013-07-10 上海交通大学医学院 充质干细胞及其提取方法在制备银屑病的药物中的应用
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WO2015110082A1 (fr) * 2014-01-27 2015-07-30 首都医科大学附属北京口腔医院 Cellules souches odontogènes et utilisation de cellules souches ondontogènes génétiquement modifiées
US20170216362A1 (en) * 2016-01-29 2017-08-03 Tokyo Women's Medical University Cell sheet composition for inhibiting progression of renal disorder, method of producing the same, and method of inhibiting progression of renal disorder using the same

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