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- Title
Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction.
- Authors
Young-sup Yoon; Wecker, Andrea; Heyd, Lindsay; Jong-Seon Park; Tkebuchava, Tengiz; Kengo Kusano; Hanley, Allison; Scadova, Heather; Gangjian Qin; Dong-Hyun Cha; Johnson, Kirby L.; Aikawa, Ryuichi; Asahara, Takayuki; Losordo, Douglas W.
- Abstract
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 doubtings 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 ofhBMSCs 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.
- Subjects
STEM cells; MYOCARDIAL infarction; HEART diseases; IMMUNE system; CYTOKINES; CELL populations
- Publication
Journal of Clinical Investigation, 2005, Vol 115, Issue 2, p326
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI200522326