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윤영섭 (Young-sup Yoon)
Tufts University School of Medicine
                 [2007년 6월] 조회수 : 8971

J. Clin. Invest.

Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction

Young-sup Yoon1, Andrea Wecker1, Lindsay Heyd1, Jong-Seon Park1, Tengiz Tkebuchava1, Kengo Kusano1, Allison Hanley1, Heather Scadova1, Gangjian Qin1, Dong-Hyun Cha2, Kirby L. Johnson2, Ryuichi Aikawa1, Takayuki Asahara1 and Douglas W. Losordo1

1Divisions of Cardiovascular Medicine and Cardiovascular Research, Caritas St. Elizabeth’s Medical Center, and 2Division of Genetics, Department of Pediatrics, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.

Young-sup Yoon, M.D, Ph.D. Director of Stem Cell Biology Division of Cardiovascular Research Caritas St. Elizabeth’s Medical Center Associate Professor of Medicine Tufts University School of Medicine 736 Cambridge Street, CBR #308, Boston

We have identified a subpopulation of stem cells within adult human BM, isolated at the single-cell level, that self-renew without loss of multipotency for more than 140 population doublings and exhibit the capacity for differentiation into cells of all 3 germ layers. Based on surface marker expression, these clonally expanded human BM-derived multipotent stem cells (hBMSCs) do not appear to belong to any previously described BM-derived stem cell population. Intramyocardial transplantation of hBMSCs after myocardial infarction resulted in robust engraftment of transplanted cells, which exhibited colocalization with markers of cardiomyocyte (CMC), EC, and smooth muscle cell (SMC) identity, consistent with differentiation of hBMSCs into multiple lineages in vivo. Furthermore, upregulation of paracrine factors including angiogenic cytokines and antiapoptotic factors, and proliferation of host ECs and CMCs, were observed in the hBMSC-transplanted hearts. Coculture of hBMSCs with CMCs, ECs, or SMCs revealed that phenotypic changes of hBMSCs result from both differentiation and fusion. Collectively, the favorable effect of hBMSC transplantation after myocardial infarction appears to be due to augmentation of proliferation and preservation of host myocardial tissues as well as differentiation of hBMSCs for tissue regeneration and repair. To our knowledge, this is the first demonstration that a specific population of multipotent human BM-derived stem cells can induce both therapeutic neovascularization and endogenous and exogenous cardiomyogenesis.

Keyword : stem cell
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