JP2020531028A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2020531028A5 JP2020531028A5 JP2020511361A JP2020511361A JP2020531028A5 JP 2020531028 A5 JP2020531028 A5 JP 2020531028A5 JP 2020511361 A JP2020511361 A JP 2020511361A JP 2020511361 A JP2020511361 A JP 2020511361A JP 2020531028 A5 JP2020531028 A5 JP 2020531028A5
- Authority
- JP
- Japan
- Prior art keywords
- cells
- human
- nrp1
- reactive
- agent
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 claims description 118
- 210000000130 stem cell Anatomy 0.000 claims description 68
- 230000002861 ventricular Effects 0.000 claims description 66
- 102000004207 Neuropilin-1 Human genes 0.000 claims description 61
- 108090000772 Neuropilin-1 Proteins 0.000 claims description 61
- 239000003795 chemical substances by application Substances 0.000 claims description 56
- 210000004027 cell Anatomy 0.000 claims description 53
- 210000005260 human cell Anatomy 0.000 claims description 22
- 210000001778 pluripotent stem cell Anatomy 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 239000003550 marker Substances 0.000 claims description 12
- 230000000747 cardiac effect Effects 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 10
- 239000003446 ligand Substances 0.000 claims description 8
- 102100037904 CD9 antigen Human genes 0.000 claims description 4
- 102000000905 Cadherin Human genes 0.000 claims description 4
- 108050007957 Cadherin Proteins 0.000 claims description 4
- 206010048610 Cardiotoxicity Diseases 0.000 claims description 4
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims description 4
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims description 4
- 102100039820 Frizzled-4 Human genes 0.000 claims description 4
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 claims description 4
- 101000885581 Homo sapiens Frizzled-4 Proteins 0.000 claims description 4
- 101001042362 Homo sapiens Leukemia inhibitory factor receptor Proteins 0.000 claims description 4
- 101000994437 Homo sapiens Protein jagged-1 Proteins 0.000 claims description 4
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 claims description 4
- 101000638251 Homo sapiens Tumor necrosis factor ligand superfamily member 9 Proteins 0.000 claims description 4
- 102100024392 Insulin gene enhancer protein ISL-1 Human genes 0.000 claims description 4
- 102100021747 Leukemia inhibitory factor receptor Human genes 0.000 claims description 4
- 102100032702 Protein jagged-1 Human genes 0.000 claims description 4
- 102000013008 Semaphorin-3A Human genes 0.000 claims description 4
- 108010090319 Semaphorin-3A Proteins 0.000 claims description 4
- 102100038081 Signal transducer CD24 Human genes 0.000 claims description 4
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 claims description 4
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 4
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 claims description 4
- 231100000259 cardiotoxicity Toxicity 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 4
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 4
- 108020001507 fusion proteins Proteins 0.000 claims description 4
- 102000037865 fusion proteins Human genes 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 4
- 210000004263 induced pluripotent stem cell Anatomy 0.000 claims description 4
- 108010090448 insulin gene enhancer binding protein Isl-1 Proteins 0.000 claims description 4
- 231100000419 toxicity Toxicity 0.000 claims description 4
- 230000001988 toxicity Effects 0.000 claims description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 claims description 3
- 208000020446 Cardiac disease Diseases 0.000 claims description 2
- 206010010356 Congenital anomaly Diseases 0.000 claims description 2
- 108010068426 Contractile Proteins Proteins 0.000 claims description 2
- 101100540419 Danio rerio kdrl gene Proteins 0.000 claims description 2
- 102100027875 Homeobox protein Nkx-2.5 Human genes 0.000 claims description 2
- 101000632197 Homo sapiens Homeobox protein Nkx-2.5 Proteins 0.000 claims description 2
- 101710107751 Myelin expression factor 2 Proteins 0.000 claims description 2
- 101150114527 Nkx2-5 gene Proteins 0.000 claims description 2
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims description 2
- 101100460507 Xenopus laevis nkx-2.5 gene Proteins 0.000 claims description 2
- 210000001557 animal structure Anatomy 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 238000004113 cell culture Methods 0.000 claims description 2
- 239000002771 cell marker Substances 0.000 claims description 2
- 230000004069 differentiation Effects 0.000 claims description 2
- 208000019622 heart disease Diseases 0.000 claims description 2
- 230000004217 heart function Effects 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims description 2
- 238000012216 screening Methods 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims 1
- 238000002955 isolation Methods 0.000 description 4
- 238000010187 selection method Methods 0.000 description 2
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2023076094A JP2023093754A (ja) | 2017-08-23 | 2023-05-02 | ニューロピリン－１（ｎｒｐ１）のヒト心室前駆細胞を単離するための細胞表面マーカーとしての使用 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762549345P | 2017-08-23 | 2017-08-23 | |
| US62/549,345 | 2017-08-23 | ||
| PCT/IB2018/001026 WO2019038587A1 (en) | 2017-08-23 | 2018-08-22 | USE OF NEUROPILIN-1 (NRP1) AS A CELL SURFACE MARKER FOR ISOLATING HUMAN CARDIAC VENTRICULAR PROGENITOR CELLS |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023076094A Division JP2023093754A (ja) | 2017-08-23 | 2023-05-02 | ニューロピリン－１（ｎｒｐ１）のヒト心室前駆細胞を単離するための細胞表面マーカーとしての使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020531028A JP2020531028A (ja) | 2020-11-05 |
| JP2020531028A5 true JP2020531028A5 (OSRAM) | 2021-09-30 |
| JP7275109B2 JP7275109B2 (ja) | 2023-05-17 |
Family
ID=63794530
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020511361A Active JP7275109B2 (ja) | 2017-08-23 | 2018-08-22 | ニューロピリン－１（ｎｒｐ１）のヒト心室前駆細胞を単離するための細胞表面マーカーとしての使用 |
| JP2023076094A Pending JP2023093754A (ja) | 2017-08-23 | 2023-05-02 | ニューロピリン－１（ｎｒｐ１）のヒト心室前駆細胞を単離するための細胞表面マーカーとしての使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023076094A Pending JP2023093754A (ja) | 2017-08-23 | 2023-05-02 | ニューロピリン－１（ｎｒｐ１）のヒト心室前駆細胞を単離するための細胞表面マーカーとしての使用 |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US11186820B2 (OSRAM) |
| EP (2) | EP3487988B1 (OSRAM) |
| JP (2) | JP7275109B2 (OSRAM) |
| CN (1) | CN111133099B (OSRAM) |
| CA (1) | CA3072579A1 (OSRAM) |
| DK (1) | DK3487988T3 (OSRAM) |
| WO (1) | WO2019038587A1 (OSRAM) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10596200B2 (en) | 2014-08-22 | 2020-03-24 | Procella Therapeutics Ab | Use of LIFR or FGFR3 as a cell surface marker for isolating human cardiac ventricular progenitor cells |
| WO2017172086A1 (en) | 2016-02-19 | 2017-10-05 | Leung Chuen Yan | Genetic markers for engraftment of human cardiac ventricular progenitor cells |
| US10508263B2 (en) | 2016-11-29 | 2019-12-17 | Procella Therapeutics Ab | Methods for isolating human cardiac ventricular progenitor cells |
| WO2019038587A1 (en) | 2017-08-23 | 2019-02-28 | Procella Therapeutics Ab | USE OF NEUROPILIN-1 (NRP1) AS A CELL SURFACE MARKER FOR ISOLATING HUMAN CARDIAC VENTRICULAR PROGENITOR CELLS |
| WO2021033699A1 (ja) | 2019-08-20 | 2021-02-25 | 国立大学法人京都大学 | 心筋細胞の富化方法 |
| CN113046308A (zh) * | 2021-03-05 | 2021-06-29 | 苏州大学附属第二医院 | 促进心脏损伤后修复的一类新型成纤维细胞及其标识方法 |
| WO2023278382A1 (en) | 2021-06-29 | 2023-01-05 | Staffan Holmin | Endoluminal delivery cannula |
| US20230330264A1 (en) | 2022-04-15 | 2023-10-19 | Smartcella Solutions Ab | COMPOSITIONS AND METHODS FOR EXOSOME-MEDIATED DELIVERY OF mRNA AGENTS |
| CN114752688B (zh) * | 2022-04-28 | 2024-02-23 | 北京大学口腔医学院 | 鉴定人类胚胎骨髓来源的间充质干细胞的方法、探针和试剂盒及其用途 |
| GB202314218D0 (en) | 2023-09-18 | 2023-11-01 | Astrazeneca Ab | Cell therapy |
| CN120699894A (zh) * | 2024-03-25 | 2025-09-26 | 中国科学院分子细胞科学卓越创新中心 | Clusterin阳性心脏类器官及其应用 |
Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5843780A (en) | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
| US5561384A (en) | 1995-11-08 | 1996-10-01 | Advanced Micro Devices, Inc. | Input/output driver circuit for isolating with minimal power consumption a peripheral component from a core section |
| US5994619A (en) | 1996-04-01 | 1999-11-30 | University Of Massachusetts, A Public Institution Of Higher Education Of The Commonwealth Of Massachusetts, As Represented By Its Amherst Campus | Production of chimeric bovine or porcine animals using cultured inner cell mass cells |
| US5945577A (en) | 1997-01-10 | 1999-08-31 | University Of Massachusetts As Represented By Its Amherst Campus | Cloning using donor nuclei from proliferating somatic cells |
| US7166280B2 (en) | 2000-04-06 | 2007-01-23 | Franco Wayne P | Combination growth factor therapy and cell therapy for treatment of acute and chronic heart disease |
| EP1435977A4 (en) | 2001-09-19 | 2005-06-08 | Ford Henry Health System | HEART TRANSPLANTATION OF STEM CELLS FOR THE TREATMENT OF HEART FAILURE |
| CA2514810A1 (en) | 2003-01-31 | 2004-08-19 | The Regents Of The University Of California | Use of islet 1 as a marker for isolating or generating stem cells |
| DE602005012081D1 (de) | 2005-07-29 | 2009-02-12 | Univ Bonn | Verfahren zur Isolierung von Stammzellen aus ein kissenformiges Gewebe der Zähne |
| US20080038229A1 (en) | 2006-08-08 | 2008-02-14 | Minguell Jose J | Intracoronary injection of a mixture of autologous bone marrow derived mononuclear cells and autologous bone marrow derived mesenchymal stem cells for utilization and rescue of infarcted myocardium |
| US20100166714A1 (en) | 2006-11-02 | 2010-07-01 | The General Hospital Corporation | Cardiovascular stem cells, methods for stem cell isolation, and uses thereof |
| WO2008058273A2 (en) | 2006-11-09 | 2008-05-15 | The Johns Hopkins University | Dedifferentiation of adult mammalian cardiomyocytes into cardiac stem cells |
| US20080182328A1 (en) | 2006-12-19 | 2008-07-31 | The Burnham Institute | Mammalian extraembryonic endoderm cells and methods of isolation |
| JP2010517578A (ja) | 2007-02-09 | 2010-05-27 | ザ ジェネラル ホスピタル コーポレイション | Ｉｓｌｅｔ１＋系統に入るように細胞を誘導する方法およびそれを拡大する方法 |
| WO2009017460A1 (en) | 2007-07-31 | 2009-02-05 | Es Cell International Pte Ltd | Method for identifying and selecting cardiomyocytes |
| EP2245140A2 (en) | 2007-11-30 | 2010-11-03 | New York Medical College | Compositions comprising hdac inhibitors and methods of their use in restoring stem cell function and preventing heart failure |
| EP2238162A1 (en) * | 2008-01-24 | 2010-10-13 | The Government of the United States of America as represented by The Secretary of the Department of Health and Human Services | Induced internalization of surface receptors |
| WO2010042856A2 (en) | 2008-10-09 | 2010-04-15 | The General Hospital Corporation | Tissue engineered myocardium and methods of production and uses thereof |
| WO2010144678A2 (en) | 2009-06-10 | 2010-12-16 | The General Hospital Corporation | Generation of vascularized human heart tissue and uses thereof |
| EP2494032A4 (en) * | 2009-10-29 | 2013-06-05 | Univ Mcmaster | GENERATION OF INDUCED PLURIPOTENTER STEM CELLS AND FIBROBLAST PRECURSOR CELLS |
| WO2011091945A1 (en) * | 2010-01-26 | 2011-08-04 | Université Libre de Bruxelles | Tools for isolating and following cardiovascular progenitor cells |
| US20130209415A1 (en) | 2010-06-03 | 2013-08-15 | The Board Of Trustees Of The Leland Stanford Junior University | Purified compositions of cardiovascular progenitor cells |
| US20120009158A1 (en) | 2010-06-18 | 2012-01-12 | The General Hospital Corporation | VENTRICULAR INDUCED PLURIPOTENT STEM (ViPS) CELLS FOR GENERATION OF AUTOLOGOUS VENTRICULAR CARDIOMYOCYTES AND USES THEREOF |
| WO2012006503A1 (en) * | 2010-07-09 | 2012-01-12 | Genentech, Inc. | Anti-neuropilin antibodies and methods of use |
| AU2010100830A4 (en) | 2010-08-03 | 2010-09-16 | Robert Fallshaw | Biased Pin Lock |
| WO2012070014A2 (en) | 2010-11-26 | 2012-05-31 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Identification of novel cell surface markers for pancreatic progenitor cells and definite endodermal cells |
| EP2647384B1 (en) | 2010-12-02 | 2018-05-23 | Riken | IMMUNOTHERAPY USING ALLO-NKT CELLS, CELLS FOR IMMUNOTHERAPY IN WHICH alpha CHAIN OF T-CELL RECEPTOR (TCR) GENE HAS BEEN REARRANGED TO UNIFORM V alpha-J alpha , AND BANKING OF NKT CELLS DERIVED FROM SAID CELLS |
| CA2829804A1 (en) * | 2011-03-29 | 2012-10-04 | Geron Corporation | Enriched populations of cardiomyocyte lineage cells from pluripotent stem cells |
| KR101323650B1 (ko) * | 2011-05-04 | 2013-11-05 | 연세대학교 산학협력단 | 미분화 전능성 줄기세포의 제거방법 |
| WO2012162740A1 (en) | 2011-05-31 | 2012-12-06 | Sonomedical Pty Ltd | Electronic monitoring system for the production of data packages for analytic and diagnostic purposes |
| WO2012162741A1 (en) | 2011-06-01 | 2012-12-06 | Monash University | Enrichment of cardiomyocytes |
| US8951798B2 (en) | 2011-10-13 | 2015-02-10 | Wisconsin Alumni Research Foundation | Generation of cardiomyocytes from human pluripotent stem cells |
| CA2861107A1 (en) * | 2012-01-13 | 2013-07-18 | President And Fellows Of Harvard College | Controlled delivery of tlr agonists in structural polymeric devices |
| JP5920741B2 (ja) | 2012-03-15 | 2016-05-18 | ｉＨｅａｒｔ Ｊａｐａｎ株式会社 | 人工多能性幹細胞から心筋および血管系混合細胞群を製造する方法 |
| US9234176B2 (en) | 2012-11-13 | 2016-01-12 | The Board Of Trustees Of The Leland Stanford Junior University | Chemically defined production of cardiomyocytes from pluripotent stem cells |
| WO2014150602A1 (en) | 2013-03-15 | 2014-09-25 | Fate Therapeutics, Inc. | Cell potency assay for therapeutic potential |
| US20150079626A1 (en) | 2013-03-19 | 2015-03-19 | Lsip, Llc | Method of obtaining a cell population containing cancer stem cells |
| US10888588B2 (en) * | 2013-10-18 | 2021-01-12 | Icahn School Of Medicine At Mount Sinai | Directed cardiomyocyte differentiation and ventricular specification of stem cells |
| ES2689804T3 (es) | 2013-11-20 | 2018-11-15 | Miltenyi Biotec Gmbh | Composiciones de subpoblaciones de cardiomiocitos |
| US9987310B2 (en) * | 2013-11-27 | 2018-06-05 | University Of Louisville Research Foundation, Inc. | Cardiac progenitor cells and methods of use therefor |
| EP3105253B1 (en) | 2014-02-12 | 2018-06-27 | F. Hoffmann-La Roche AG | Anti-jagged1 antibodies and methods of use |
| CA2940691C (en) | 2014-03-11 | 2022-10-25 | Indiana University Research And Technology Corporation | Method for generating endothelial colony forming cell-like cells |
| WO2015166638A1 (ja) * | 2014-05-01 | 2015-11-05 | ｉＨｅａｒｔ Ｊａｐａｎ株式会社 | Ｃｄ８２陽性心筋前駆細胞 |
| US10144916B2 (en) * | 2014-05-09 | 2018-12-04 | Becton, Dickinson And Company | Cell surface signature for processing cardiomyocyte subsets from heterogeneous cell samples |
| US10596200B2 (en) | 2014-08-22 | 2020-03-24 | Procella Therapeutics Ab | Use of LIFR or FGFR3 as a cell surface marker for isolating human cardiac ventricular progenitor cells |
| DK3183337T3 (en) | 2014-08-22 | 2019-04-01 | Procella Therapeutics Ab | Use of Jagged 1 / Frizzled 4 as cell surface marker for isolation of human cardiac ventricular progenitor cells |
| US9765299B2 (en) | 2014-09-10 | 2017-09-19 | Wisconsin Alumni Research Foundation | Chemically defined albumin-free conditions for cardiomyocyte differentiation of human pluripotent stem cells |
| CN107108743B (zh) | 2014-12-03 | 2021-05-04 | (株)爱恩德生物 | 结合神经毡蛋白1的抗体及其用途 |
| WO2016131137A1 (en) * | 2015-02-17 | 2016-08-25 | University Health Network | Methods for making and using sinoatrial node-like pacemaker cardiomyocytes and ventricular-like cardiomyocytes |
| WO2017172086A1 (en) | 2016-02-19 | 2017-10-05 | Leung Chuen Yan | Genetic markers for engraftment of human cardiac ventricular progenitor cells |
| US10508263B2 (en) | 2016-11-29 | 2019-12-17 | Procella Therapeutics Ab | Methods for isolating human cardiac ventricular progenitor cells |
| WO2019038587A1 (en) | 2017-08-23 | 2019-02-28 | Procella Therapeutics Ab | USE OF NEUROPILIN-1 (NRP1) AS A CELL SURFACE MARKER FOR ISOLATING HUMAN CARDIAC VENTRICULAR PROGENITOR CELLS |
-
2018
- 2018-08-22 WO PCT/IB2018/001026 patent/WO2019038587A1/en not_active Ceased
- 2018-08-22 CA CA3072579A patent/CA3072579A1/en active Pending
- 2018-08-22 CN CN201880054988.6A patent/CN111133099B/zh active Active
- 2018-08-22 JP JP2020511361A patent/JP7275109B2/ja active Active
- 2018-08-22 EP EP18783080.7A patent/EP3487988B1/en active Active
- 2018-08-22 EP EP19210435.4A patent/EP3663393A1/en not_active Withdrawn
- 2018-08-22 DK DK18783080.7T patent/DK3487988T3/da active
- 2018-08-22 US US16/109,218 patent/US11186820B2/en active Active
-
2021
- 2021-10-21 US US17/507,454 patent/US12404488B2/en active Active
-
2023
- 2023-05-02 JP JP2023076094A patent/JP2023093754A/ja active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2017525393A5 (OSRAM) | ||
| JP6937821B2 (ja) | 生体組織から単離できる多能性幹細胞 | |
| TWI288779B (en) | Dedifferentiated, programmable stem cells of monocytic origin, and their production and use | |
| JP2022027790A (ja) | ヒト胚性幹細胞由来血管芽細胞からナチュラルキラー細胞および樹状細胞を生成する方法 | |
| JP5283120B2 (ja) | Ｅｓ細胞からの造血前駆細胞を内包する構造物、及び該構造物を用いた血球細胞の調製方法。 | |
| JP7275109B2 (ja) | ニューロピリン－１（ｎｒｐ１）のヒト心室前駆細胞を単離するための細胞表面マーカーとしての使用 | |
| JP6491606B2 (ja) | 多機能未成熟歯髄幹細胞および療法適用 | |
| CN109722415A (zh) | 一种造血干细胞的培养组合物、培养基以及造血干细胞的培养方法 | |
| Zhang et al. | Peripheral blood stem cells: phenotypic diversity and potential clinical applications | |
| ES2394261T3 (es) | Materiales y métodos relacionados con terapias basadas en células | |
| CN111918963A (zh) | 表达趋化因子受体和细胞粘附分子的cd3阴性细胞群体及其用途和制备方法 | |
| TW201512399A (zh) | Ｎｋ細胞的調製方法 | |
| CN103442724A (zh) | 含有可从机体组织中分离的ssea-3阳性的多能干细胞的同种异体移植用细胞治疗用组合物 | |
| Demirci et al. | Definitive hematopoietic stem/progenitor cells from human embryonic stem cells through serum/feeder-free organoid-induced differentiation | |
| JP2019535299A (ja) | ヒト心室前駆細胞を単離するための方法 | |
| EP3076980A1 (en) | A method of treating neoplasia | |
| JP6935654B2 (ja) | 合成ペプチドを用いた心筋細胞の生産方法 | |
| CN109890805A (zh) | 用于造血干细胞和祖细胞的产生、增殖和分化的取代的唑衍生物 | |
| CN108118025A (zh) | 一种基于定性滤纸的三维肝模型的建立及其应用 | |
| WO2024117199A1 (ja) | 組成物、細胞の生産方法、細胞、細胞の培養方法および組成物の生産方法 | |
| Batten et al. | Immune response to stem cells and strategies to induce tolerance | |
| Perlea et al. | Phenotype heterogeneity in dental pulp stem niches | |
| JP2016523514A (ja) | 心臓内膜由来の成体幹細胞及びこれの製造方法 | |
| JP6695795B2 (ja) | 造血細胞の増殖ペプチドおよびその用途 | |
| Popov et al. | Spontaneous transformation and immortalization of mesenchymal stem cells in vitro |