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PMID: 15690083 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 115 ·No. 2 ·2005-02-00 ·Pages 326-38

Yoon YS, Wecker A, Heyd L, Park JS, Tkebuchava T, Kusano K, Hanley A, Scadova H, Qin G, Cha DH, Johnson KL, Aikawa R, Asahara T, Losordo DW

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 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.

MeSH Terms
Adult Animals Bone Marrow Cells/cytology,physiology Cell Differentiation/physiology Cell Lineage/physiology Cell Proliferation Cells, Cultured Female Heart/physiology Humans Male Multipotent Stem Cells/physiology,transplantation Myocardial Infarction/pathology,therapy Myocardium/pathology Myocytes, Cardiac/pathology,physiology Myocytes, Smooth Muscle/pathology,physiology Neovascularization, Physiologic/physiology Rats Rats, Nude Regeneration/physiology
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Yoon Young-sup
Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Boston, Massachusetts 02135, USA. young.yoon@tufts.edu
Wecker Andrea
Heyd Lindsay
Park Jong-Seon
Tkebuchava Tengiz
Kusano Kengo
Hanley Allison
Scadova Heather
Qin Gangjian
Cha Dong-Hyun
Johnson Kirby L
Aikawa Ryuichi
Asahara Takayuki
Losordo Douglas W
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI22326
Email
young.yoon@tufts.edu
Published
2005-02-00
Pages
326-38
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC546424
Subset
IM
Grants
NHLBI NIH HHS · P01 HL066957 · United States
NHLBI NIH HHS · R01 HL063414 · United States
NHLBI NIH HHS · HL63695 · United States
NHLBI NIH HHS · HL63414 · United States
NHLBI NIH HHS · HL-66957 · United States
NHLBI NIH HHS · R37 HL053354 · United States
NHLBI NIH HHS · R01 HL063695 · United States
NHLBI NIH HHS · HL53354 · United States
NHLBI NIH HHS · HL60911 · United States
NHLBI NIH HHS · R01 HL053354 · United States
External Links
PubMed source DOI: 10.1172/JCI22326 PMC Full Text View journal details
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