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

Young Sup Yoon, Andrea Wecker, Lindsay Heyd, Jong Seon Park, Tengiz Tkebuchava, Kengo Kusano, Allison Hanley, Heather Scadova, Gangjian Qin, Dong Hyun Cha, Kirby L. Johnson, Ryuichi Aikawa, Takayuki Asahara, Douglas W. Losordo

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)326-338
Number of pages13
JournalJournal of Clinical Investigation
Volume115
Issue number2
DOIs
Publication statusPublished - 2005 Feb 1

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Multipotent Stem Cells
Myocardium
Bone Marrow
Myocardial Infarction
Stem Cells
Population
Germ Layers
Adult Stem Cells
Angiogenesis Inducing Agents
Stem Cell Transplantation
Coculture Techniques
Cardiac Myocytes
Smooth Muscle Myocytes
Regeneration
Cell Differentiation
Up-Regulation
Transplantation
Cytokines

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Yoon, Young Sup ; 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. / Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 2. pp. 326-338.
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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.",
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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 2005, 'Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction', Journal of Clinical Investigation, vol. 115, no. 2, pp. 326-338. https://doi.org/10.1172/JCI200522326

Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. / Yoon, Young Sup; 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.

In: Journal of Clinical Investigation, Vol. 115, No. 2, 01.02.2005, p. 326-338.

Research output: Contribution to journalArticle

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T1 - Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction

AU - Yoon, Young Sup

AU - Wecker, Andrea

AU - Heyd, Lindsay

AU - Park, Jong Seon

AU - Tkebuchava, Tengiz

AU - Kusano, Kengo

AU - Hanley, Allison

AU - Scadova, Heather

AU - Qin, Gangjian

AU - Cha, Dong Hyun

AU - Johnson, Kirby L.

AU - Aikawa, Ryuichi

AU - Asahara, Takayuki

AU - Losordo, Douglas W.

PY - 2005/2/1

Y1 - 2005/2/1

N2 - 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.

AB - 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.

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