WO2016158670A1 - Composition pour thérapie de régénération vasculaire, contenant des cellules adipeuses dédifférenciées en tant qu'ingrédient actif - Google Patents

Composition pour thérapie de régénération vasculaire, contenant des cellules adipeuses dédifférenciées en tant qu'ingrédient actif Download PDF

Info

Publication number
WO2016158670A1
WO2016158670A1 PCT/JP2016/059386 JP2016059386W WO2016158670A1 WO 2016158670 A1 WO2016158670 A1 WO 2016158670A1 JP 2016059386 W JP2016059386 W JP 2016059386W WO 2016158670 A1 WO2016158670 A1 WO 2016158670A1
Authority
WO
WIPO (PCT)
Prior art keywords
human
dfat
cells
active ingredient
cell
Prior art date
Application number
PCT/JP2016/059386
Other languages
English (en)
Japanese (ja)
Inventor
太郎 松本
浩一郎 加野
智彦 風間
Original Assignee
学校法人日本大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 学校法人日本大学 filed Critical 学校法人日本大学
Publication of WO2016158670A1 publication Critical patent/WO2016158670A1/fr

Links

Images

Classifications

    • 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
    • A61K35/35—Fat tissue; Adipocytes; Stromal cells; Connective tissues

Definitions

  • the present invention relates to a composition for revascularization therapy.
  • the present invention relates to a composition for revascularization therapy comprising dedifferentiated fat cells (DFAT) as an active ingredient.
  • DFAT dedifferentiated fat cells
  • G-CSF mobilized peripheral blood mononuclear cells (iii) adipose tissue derived basal basal fraction (SVF) cells, (iv) peripheral blood mononuclear cells, (v) G-CSF mobilized CD34 positive cells, Similar angiogenesis therapy using many autologous cells such as vi) bone marrow-derived CD133 positive cells, (vii) cultured bone marrow mesenchymal stem cells (MSC) (viii) cultured adipose tissue-derived stem cells (ASC) has been performed.
  • MSC bone marrow mesenchymal stem cells
  • ASC cultured adipose tissue-derived stem cells
  • the cells of (i) to (vi) are not cultured, but a large amount of tissue is required to obtain the required number of cells, which is highly invasive to patients. For this reason, the number of treatments is usually limited to only one, except that the invasiveness associated with collection is relatively low (iv).
  • the cells (i) to (iv) are a diverse cell population, the transplantation effect and safety are not constant.
  • the cells of (v) and (vi) can be improved in cell uniformity by performing a sorting operation using a stem cell marker antibody, but the complexity and reduction in preparation efficiency associated with antibody selection and preparation are reduced. There is a problem that the cost becomes high.
  • the cells of (vii) are used after collecting dozens of ml of bone marrow fluid, adherently cultured and proliferated, and the cells of (viii) are subjected to enzyme treatment of adipose tissue and adherently cultured and proliferated in the same manner as (vii). Use from. Therefore, both (vii) and (viii) cells have the merit that they can be prepared in large quantities from a relatively small amount of tissue, but this method is a method of culturing and proliferating stem cells present in minute amounts in adult tissues. For this reason, contamination with other cells is unavoidable, and it is necessary to repeat the subculture several times in order to obtain the number of cells necessary for treatment. The number of treatments is usually only once.
  • rat adipose tissue-derived progenitor cells and rat adipose tissue-derived mesenchymal stem cells are effective for angiogenesis (Patent Documents 1 and 2).
  • the present inventors have succeeded for the first time in establishing dedifferentiated adipocytes (DFAT) as preadipocytes by inducing dedifferentiation of mature adipocytes derived from adipose tissue of non-human animals such as mice (patents) Reference 3), it has been shown that by inducing differentiation of DFAT, functions of osteoblasts, myoblasts, chondrocytes, nerve cells and the like can be obtained (Patent Document 4).
  • DFAT dedifferentiated adipocytes
  • Non-Patent Documents 1 to 3 mouse and rat DFAT has angiogenic ability.
  • DFAT in mice and rats is difficult to increase to the number required for transplantation because of its low growth ability after subculture, and since transformation (immortalization) occurs by subculture, it is tumorigenic. The possibility increases and it cannot be safely transplanted. For these reasons, it has been considered that the same phenomenon occurs in human DFAT as in mouse and rat DFAT and is not suitable for treatment.
  • the present invention is a cell for revascularization therapy that exhibits an excellent blood flow improvement effect compared to bone marrow MSC, ASC, etc., which are conventional treatment cells, and it is easy to obtain a sufficient amount necessary for transplantation.
  • An object of the present invention is to provide a cell for revascularization therapy having a stable quality.
  • a blood flow improving agent comprising human dedifferentiated adipocytes (human DFAT) as an active ingredient.
  • An angiogenesis promoter containing human dedifferentiated adipocytes (human DFAT) as an active ingredient.
  • a therapeutic agent for ischemic disease comprising human dedifferentiated fat cells (human DFAT) as an active ingredient.
  • human dedifferentiated adipocytes prepared from human mature adipocytes have excellent angiogenic potential, and are effective cells for cell therapy for ischemic diseases such as peripheral artery disease (PAD). Clarified that it can be a source. Therefore, the present invention has the following effects. (1) Large-scale cell preparation facilities, growth factors, and antibody selection for increasing purity are not necessary. Moreover, since a large amount can be adjusted in a short culture period, the preparation cost can be kept low. (2) Regenerative medical donor cells with high purity can be efficiently collected from a small amount of adipose tissue that can be easily collected, and the obtained cells have high angiogenic ability. (3) Multiple treatments can be performed by collecting a single tissue, and treatment that exhibits a certain level of effectiveness without being affected by donor age or underlying disease is possible. (4) Unlike existing cell sources, it can show long-term efficacy against PAD.
  • the karyotype analysis result of human DFAT is shown.
  • A Photograph of chromosome structure by Giemsa staining.
  • B The table
  • the comprehensive analysis result of the cytokine secreted in a human DFAT culture supernatant is shown.
  • Human DFAT (hDFAT), human ASC (hASC), human preadipocyte (hPreadipocyte), human fibroblast (hFibroblast), secreted cytokine (HGF, SDF-1, The quantification results of MCP-1, IL-6, VEGF, and Leptin) are shown. Figures in parentheses indicate donor age.
  • the examination result of the angiogenesis ability of a human DFAT culture supernatant is shown.
  • A Photograph showing the proliferation of vascular endothelial cells by human DFAT culture supernatant.
  • B A graph showing the total length (total lumen length) and total area (total lumen area) of the vascular lumen formed in the well by the human DFAT culture supernatant and human bone marrow MMC culture supernatant.
  • the examination result of the angiogenesis ability of the human DFAT culture supernatant by the difference in donor age is shown.
  • Donors are 2-year-old male (h-DFAT2yM), 29-year-old male (h-DFAT29yM), 56-year-old female (h-dFAT56yF), 75-year-old female (h-DFAT75yF), 82-year-old female (h-DFAT82yF).
  • the comparative examination result of the angiogenesis ability of the human DFAT culture supernatant (hDFAT) and human ASC culture supernatant (hASC) derived from the same donor is shown.
  • A Photograph showing histological observation results.
  • the effect of human DFAT transplantation in an immunodeficient mouse lower limb ischemia model is shown.
  • (B) The graph which shows the ischemic rate of the ischemic limb with respect to a mouse
  • the quantification result of secretory cytokine (HGF) in the culture supernatant of human DFAT (hDFAT) and human ASC (hASC) is shown.
  • the quantification result of secretory cytokine (VEGF) in the culture supernatant of human DFAT (hDFAT) and human ASC (hASC) is shown.
  • Human DFAT The method for adjusting human DFAT in the present invention may be performed with reference to, for example, Japanese Patent Application Laid-Open No. 2000-83656 made by the present inventors. That is, after adipose tissue such as human subcutaneous or internal organs is treated with collagenase, a single fraction consisting only of monocystic adipocytes is collected by filtration with a mesh having a diameter of 100 to 200 ⁇ m. Human dedifferentiated adipocytes (human DFAT) can be obtained by further subculturing fibroblast-like adipocytes produced by ceiling culture of these monocystic adipocytes.
  • human DFAT can also be obtained by a method of adjusting cells that do not have lipid droplets originating from mature adipocytes by culturing mature adipocytes by methods other than the above-described ceiling culture. Confirmation that the obtained cells are human DFAT can be determined, for example, based on whether or not they have the following characteristics specific to human DFAT. Human DFAT has adhesiveness to plastic and exhibits multipotency into osteoblasts, adipocytes, chondrocytes and smooth muscle cells in vitro.
  • human DFAT has lost expression of marker genes of mature adipocytes such as lipoprotein lipase and GLUT4, but expresses early differentiation marker genes of fat, bone and cartilage such as PPARg, RUNX2, and SOX9. Furthermore, human DFAT had a high cell proliferation ability, and the cell doubling time was about 65 hours for the second passage cell and about 48 hours for the tenth passage.
  • Human DFAT can be obtained from 10 ml of aspirated fat or 1 g of adipose tissue by the above-mentioned preparation method, and 10 8 cells can be obtained in primary culture for about 2 weeks. This is about 25 times the preparation efficiency of cultured ASC. Therefore, it is possible to obtain cells of the order of 10 9 by subculturing 2-3 times. Since the number of cells used for a single cell therapy is about 10 8 , treatment can be performed about 10 times if the obtained cells are subdivided and cryopreserved by collecting adipose tissue once (about 10 ml). I know that there is.
  • human DFAT can obtain homogeneous cells from primary culture.
  • Primary cultured ASC contains smooth muscle cells (18.6%), vascular endothelial cells (2.7%) and monocytes (13.3%).
  • the contamination rate of these cells in primary cultured human DFAT is It was very low as 0.1% or less.
  • human DFAT is not only subcultured but also primary culture cells are CD34 negative, and maintain stable traits compared to ASC that is CD34 positive at the start of culture but whose expression is reduced by subculture (See FIG. 9). When isolating mature adipocytes, if collagenase treatment and filtration are not performed properly and adequately, cells other than mature adipocytes attach to mature adipocytes and proliferate in ceiling culture.
  • CD34 positive cells may increase. It was also revealed that human DFAT can be prepared without being affected by donor age or underlying disease. These characteristics are thought to contribute to eliminating individual differences in performance as therapeutic cells and reducing treatment refractory cases (standardization of therapeutic cells). Furthermore, human DFAT showed a significantly higher blood flow improvement effect than peripheral blood mononuclear cells and fibroblasts in transplantation experiments to lower limb ischemia model animals described later in Examples.
  • angiogenesis refers to a phenomenon in which new blood vessels are formed from existing blood vessels.
  • physiological blood vessel development in the embryonic period, as well as cancer and diabetic properties It also occurs in pathological conditions such as retinopathy.
  • angiogenesis and vascular regeneration are used synonymously unless otherwise specified.
  • revascularization or therapeutic angiogenesis
  • ischemic diseases such as peripheral arterial disease (PAD), angina pectoris, and myocardial infarction.
  • PED peripheral arterial disease
  • the performance of cells having revascularization ability includes the expression and secretion amount of angiogenesis-promoting factors such as HGF, VEGF-A, FGF-2, SDF-1, and leptin, and vascular endothelial cells and pericytes that are vascular constituent cells. It can be confirmed by the ability to differentiate into.
  • DFAT in-house DFAT
  • DFAT in-house DFAT
  • a method of improving the blood flow by thawing this periodically and injecting it into an ischemic site (muscle) can be mentioned.
  • a DFAT cell bank for allogeneic transplantation using adipose tissue discarded by surgery or the like it is possible to construct a DFAT cell bank for allogeneic transplantation using adipose tissue discarded by surgery or the like.
  • a therapeutic model is assumed in which cryopreserved DFAT fully matched with HLA is thawed and injected into the patient's ischemic site.
  • the present invention relates to a drug for regenerating blood vessels and repairing damaged tissue caused by ischemia, comprising human DFAT of the present invention as an active ingredient.
  • the drug of the present invention may be human DFAT itself, or a pharmaceutically acceptable carrier such as a preservative or stabilizer may be added.
  • “Pharmaceutically acceptable” means a pharmaceutically acceptable material that itself does not have the above-mentioned activity and can be administered together with the above-mentioned drug.
  • parenteral administration includes parenteral administration.
  • parenteral administration include administration in the form of injections, and examples of injections include subcutaneous injections, intramuscular injections, intraperitoneal injections, and the like.
  • parenteral administration includes administration in the form of injections, and examples of injections include subcutaneous injections, intramuscular injections, intraperitoneal injections, and the like.
  • local administration may be performed targeting a part of a human body (one tissue such as an organ), or the cells of the present invention may be applied to an entire organism by administration into a blood vessel. May be circulated. Moreover, you may administer simultaneously to the target of several places.
  • the cells of the present invention can be locally administered to a region where treatment is desired. For example, it can be administered by local injection during surgery or by use of a catheter.
  • pH adjusters, buffers, stabilizers, preservatives, etc. are added as necessary, and subcutaneous, intramuscular and intravenous injections are prepared by conventional methods.
  • the dose varies depending on the patient's age, sex, weight and symptoms, therapeutic effect, administration method, treatment time, type of active ingredient contained in the cells, etc., and is not particularly limited.
  • the cells of the invention may be administered as part of a pharmaceutical composition with at least one known chemotherapeutic agent. In one embodiment, the cells of the invention and the known chemotherapeutic agent may be administered substantially simultaneously. It is also possible to administer the cell of the present invention to a part of a human removed from the human and return the part of the human to the removed human or other human.
  • Example 1 Character analysis of human DFAT (1) Karyotype analysis (1-1) Test method (i) Preparation of human DFAT This was carried out with reference to Japanese Patent Application Laid-Open No. 2000-83656 made by the present inventors. . That is, a human adipose subcutaneous human tissue was treated with collagenase, and then filtered with a mesh having a diameter of 100 to 200 ⁇ m to collect a single fraction consisting only of monocystic adipocytes. Human dedifferentiated adipocytes (human DFAT) were prepared by subculturing fibroblast-like adipocytes produced by ceiling culture of these monocystic adipocytes.
  • Example 2 Examination of angiogenic ability of human DFAT Analysis of DFAT-secreted cytokine (1) Protein array analysis of expressed cytokine (1-1) Test method (i) Preparation method of human ASC Precipitation fraction of human DFAT obtained in the same manner as in Example 1 (stromal vascular fraction) SVF cells were collected from the fractional basal fraction (SVF) and cultured for about 2 weeks in a culture flask to prepare human ASC. The method for adjusting human ASC is the same in the following test examples.
  • hPreadipocyte Human preadipocytes purchased from DS Pharma Medical Co., Ltd. were prepared by thawing, washing and adherent culture. As the medium, DMEM containing 10% FBS was used. The method for preparing human preadipocytes is the same in the following test examples.
  • hBM-MSC Human bone marrow MSC
  • DMEM containing 10% FBS was used.
  • the method for adjusting human bone marrow MSC is the same in the following test examples.
  • HGF and SDF-1 were found to be characteristically higher in expression than preadipocyte, human ASC, and human bone marrow MSC (FIG. 4).
  • Angiogenic ability of human DFAT culture supernatant in vitro (1) Comparison of human DFAT and human bone marrow MSC (hBM-MSC) (1-1) Test method Angiogenesis kit (KZ-1000, KURABO, Osaka, Japan) The in vitro angiogenesis ability of the human DFAT culture supernatant was examined.
  • This kit is a design in which human fibroblasts and human vascular endothelial cells are co-cultured in advance in a 24-well plate, and luminal formation of vascular endothelial cells is induced by culturing in a dedicated angiogenic medium. When a sample medium containing a test substance is added to this and cultured, a difference in lumen forming ability occurs.
  • the angiogenesis ability was measured by inducing tube formation according to the protocol of this kit, and tube formation was visualized by immunostaining using a mouse anti-human CD31 antibody.
  • the DFAT culture supernatant and human bone marrow MSC culture supernatant were prepared by the above method and mixed 1: 1 with the attached angiogenesis medium to obtain a sample medium.
  • Test Results The culture supernatant of human DFAT markedly promoted the proliferation and lumen formation of vascular endothelial cells.
  • the angiogenic potential of DFAT was equal to or greater than that of bone marrow MSC (FIG. 5).
  • SCID immunodeficient mice
  • the cell therapy method with respect to ischemic diseases can be provided by utilizing the human dedifferentiated fat cell (human DFAT) prepared from a human mature fat cell. .
  • human DFAT human dedifferentiated fat cell

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

La présente invention vise à fournir une cellule pour une utilisation dans une thérapie de régénération vasculaire qui présente un effet d'amélioration de la circulation sanguine supérieur relativement à une CSM dérivée de la moelle osseuse, une SCA ou équivalent, étant une cellule classiquement utilisée en thérapie, et qui peut être obtenue facilement en une quantité suffisante pour la transplantation tout en ayant une qualité stable. On a découvert découvert qu'une DFAT humaine présente une grande aptitude à la néovascularisation, peut présenter une capacité de prolifération élevée après avoir été l'objet d'un repiquage et peut par conséquent être produite facilement en une quantité nécessaire pour une transplantation, sans subir de transformation. On a par conséquent découvert pour la première fois qu'une DFAT (cellule adipeuse dédifférenciée) humaine est efficace pour une thérapie de régénération vasculaire d'un corps humain. Cette découverte a conduit à l'accomplissement de la présente invention. En d'autres termes, la présente invention concerne un agent d'amélioration de la circulation sanguine contenant des cellules adipeuses dédifférenciées humaines (DFAT humaines) en tant que principe actif.
PCT/JP2016/059386 2015-03-27 2016-03-24 Composition pour thérapie de régénération vasculaire, contenant des cellules adipeuses dédifférenciées en tant qu'ingrédient actif WO2016158670A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2015-065598 2015-03-27
JP2015065598A JP2018087141A (ja) 2015-03-27 2015-03-27 脱分化脂肪細胞を有効成分とする血管再生療法用組成物

Publications (1)

Publication Number Publication Date
WO2016158670A1 true WO2016158670A1 (fr) 2016-10-06

Family

ID=57005811

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2016/059386 WO2016158670A1 (fr) 2015-03-27 2016-03-24 Composition pour thérapie de régénération vasculaire, contenant des cellules adipeuses dédifférenciées en tant qu'ingrédient actif

Country Status (2)

Country Link
JP (1) JP2018087141A (fr)
WO (1) WO2016158670A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2020066624A (ja) * 2018-10-18 2020-04-30 学校法人日本大学 壊死性腸炎治療用組成物

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007504204A (ja) * 2003-09-05 2007-03-01 サントル　ナショナル　ドゥ　ラ　ルシェルシュ　シアンティフィク 機能的な血管ネットワークの形成を開始するための脂肪組織細胞の使用

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007504204A (ja) * 2003-09-05 2007-03-01 サントル　ナショナル　ドゥ　ラ　ルシェルシュ　シアンティフィク 機能的な血管ネットワークの形成を開始するための脂肪組織細胞の使用

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
CASTEILLA L. ET AL.: "Plasticity of human adipose lineage cellstoward endothelial cells: physiological and therapeutic perspectives", CIRCULATION, vol. 109, 2004, pages 656 - 663, XP009034616 *
HIDEOMI KAWAUCHI ET AL.: "Kekkan Geka to Kiso Kenkyu Datsubunka Shibo Saibo o Mochiita Buta Kyoketsushi ni Taisuru Jika Saibo Ishoku Chiryo no Kento", KEKKAN GEKA, vol. 32, no. 1, 2013, pages 18 - 24 *
JUMABAY M. ET AL.: "Endothelial differentiation in multipotent cells derived from mouse and human white mature adipocytes", J. MOL. CELL . CARDIOL., vol. 53, no. 6, 2012, pages 790 - 800, XP055319355 *
KOU L. ET AL.: "The phenotype and tissue- specific nature of multipotent cells derived from human mature adipocytes", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 444, 2014, pages 543 - 548, XP028665411 *
SONG N. ET AL.: "The perivascular phenotype and behaviors of dedifferentiated cells derived from human mature adipocytes", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 457, no. 3, 13 February 2015 (2015-02-13), pages 479 - 484, XP055319353 *
TARO MATSUMOTO: "Shibo Soshiki Yurai Kansaibo Ryoho no Kiso Datsubunka Shibo Saibo(DFAT", CLINICAL EVALUATION, vol. 38, no. 4, 2011, pages 761 - 765 *
TARO MATSUMOTO: "Shibo Yurai Kansaibo no Rinsho Oyo eno Tenkai Biological characterization and potential clinical applications of dedifferentiated fat (DFAT) cells", JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, vol. 242, no. 4, 2012, pages 326 - 331 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2020066624A (ja) * 2018-10-18 2020-04-30 学校法人日本大学 壊死性腸炎治療用組成物
JP7348612B2 (ja) 2018-10-18 2023-09-21 学校法人日本大学 壊死性腸炎治療用組成物

Also Published As

Publication number Publication date
JP2018087141A (ja) 2018-06-07

Similar Documents

Publication Publication Date Title
Bao et al. C-Kit Positive cardiac stem cells and bone marrow–derived mesenchymal stem cells synergistically enhance angiogenesis and improve cardiac function after myocardial infarction in a paracrine manner
Moon et al. Human adipose tissue-derived mesenchymal stem cells improve postnatal neovascularization in a mouse model of hindlimb ischemia
Javazon et al. Enhanced epithelial gap closure and increased angiogenesis in wounds of diabetic mice treated with adult murine bone marrow stromal progenitor cells
Dai et al. Potential implications of mesenchymal stem cells in cancer therapy
JP5968442B2 (ja) 心筋梗塞の修復再生を誘導する多能性幹細胞
Li et al. CXCR4 positive bone mesenchymal stem cells migrate to human endothelial cell stimulated by ox-LDL via SDF-1α/CXCR4 signaling axis
Bony et al. Adipose mesenchymal stem cells isolated after manual or water-jet-assisted liposuction display similar properties
JP2008504290A (ja) 虚血の細胞ベースの治療
EP2902483B1 (fr) Procédé de prolifération in vitro d'une population cellulaire contenant des cellules appropriées pour traiter une maladie ischémique
EP1771551B1 (fr) Nouvelles populations cellulaires et utilisations de celles-ci
Spitkovsky et al. Adult mesenchymal stromal stem cells for therapeutic applications
Swart et al. Mesenchymal stromal cells for treatment of arthritis
US20070053884A1 (en) Novel adult tissue-derived stem cell and use thereof
Hou et al. Erythropoietin augments the efficacy of therapeutic angiogenesis induced by allogenic bone marrow stromal cells in a rat model of limb ischemia
EP3643316A1 (fr) Agent de traitement de l' épidermolyse bulleuse
Wang et al. Pre-clinical study of human umbilical cord mesenchymal stem cell transplantation for the treatment of traumatic brain injury: safety evaluation from immunogenic and oncogenic perspectives
WO2016158670A1 (fr) Composition pour thérapie de régénération vasculaire, contenant des cellules adipeuses dédifférenciées en tant qu'ingrédient actif
JP7546193B2 (ja) 細胞群及びその取得方法
JP6250706B2 (ja) 変形性関節症の予防または治療における異系間質血管層細胞および異系間葉前駆細胞の使用
WO2024128222A1 (fr) Composition et utilisation associée
US20240024370A1 (en) Pharmaceutical composition including adipose-derived regenerative cells (adrcs) for use in prevention and treatment of liver fibrosis or liver cirrhosis
WO2024128224A1 (fr) Composition pour amplifier la capacité de cellules souches mésenchymateuses à se différencier en adipocytes
Kunter et al. Potential risks of stem cell therapies
Wilson Determining the Effects of Aging on Murine Bone-Marrow Derived Mesenchymal Stem Cell Cardiac and Angiogenic Plasticity Potential
Fazel Cardiac repair and not regeneration after myocardial infarction: the role and therapeutic utility of the c-kitSCF pathway.

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16772551

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16772551

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP