| Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. | |
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MedLine Citation:
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PMID: 19666564 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC) remain highly controversial. Here we tested the hypothesis that MSCs regenerate chronically infarcted myocardium through mechanisms comprising long-term engraftment and trilineage differentiation. Twelve weeks after myocardial infarction, female swine received catheter-based transendocardial injections of either placebo (n = 4) or male allogeneic MSCs (200 million; n = 6). Animals underwent serial cardiac magnetic resonance imaging, and in vivo cell fate was determined by co-localization of Y-chromosome (Y(pos)) cells with markers of cardiac, vascular muscle, and endothelial lineages. MSCs engrafted in infarct and border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4, Nkx2.5, and alpha-sarcomeric actin. In addition, Y(pos) MSCs exhibited vascular smooth muscle and endothelial cell differentiation, contributing to large and small vessel formation. Infarct size was reduced from 19.3 +/- 1.7% to 13.9 +/- 2.0% (P < 0.001), and ejection fraction (EF) increased from 35.0 +/- 1.7% to 41.3 +/- 2.7% (P < 0.05) in MSC but not placebo pigs over 12 weeks. This was accompanied by increases in regional contractility and myocardial blood flow (MBF), particularly in the infarct border zone. Importantly, MSC engraftment correlated with functional recovery in contractility (R = 0.85, P < 0.05) and MBF (R = 0.76, P < 0.01). Together these findings demonstrate long-term MSC survival, engraftment, and trilineage differentiation following transplantation into chronically scarred myocardium. MSCs are an adult stem cell with the capacity for cardiomyogenesis and vasculogenesis which contribute, at least in part, to their ability to repair chronically scarred myocardium. |
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Authors:
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Henry C Quevedo; Konstantinos E Hatzistergos; Behzad N Oskouei; Gary S Feigenbaum; Jose E Rodriguez; David Valdes; Pradip M Pattany; Juan P Zambrano; Qinghua Hu; Ian McNiece; Alan W Heldman; Joshua M Hare |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-08-05 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 106 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-26 Completed Date: 2009-10-08 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 14022-7 Citation Subset: IM |
Affiliation:
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Interdisciplinary Stem Cell Institute and Department of Medicine, Cardiovascular Division, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism Animals Bone Marrow Cells Cardiomyopathies / pathology* Cell Differentiation Cell Survival Female GATA4 Transcription Factor / metabolism Homeodomain Proteins / metabolism Ischemia / pathology* Male Mesenchymal Stem Cells / cytology* Placebos Swine Swine, Miniature Transcription Factors / metabolism Y Chromosome / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01-HL084275/HL/NHLBI NIH HHS; U54-HL081028/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/GATA4 Transcription Factor; 0/Homeodomain Proteins; 0/Nkx2-5 protein, mouse; 0/Placebos; 0/Transcription Factors |
| Comments/Corrections | |
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