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Cell fusion contributes to the rescue of apoptotic cardiomyocytes by bone marrow cells.
MedLine Citation:
PMID:  22805279     Owner:  NLM     Status:  Publisher    
Cardiomyocyte apoptosis is an important contributor to the progressive cardiac dysfunction that culminates in congestive heart failure. Bone marrow cells (BMCs) restore cardiac function following ischemia, and transplanted BMCs have been reported to fuse with cells of diverse tissues. We previously demonstrated that the myogenic conversion of bone marrow stromal cells increased nearly two-fold when the cells were co-cultured with apoptotic (TNF-α treated) cardiomyocytes. We therefore hypothesized that cell fusion may be a major mechanism by which BMCs rescue cardiomyocytes from apoptosis. We induced cellular apoptosis in neonatal rat cardiomyocytes by treatment with hydrogen peroxide (H(2) O(2) ). The TUNEL assay demonstrated an increase in apoptosis from 4.5±1.3% in non-treated cells to 19.0±4.4% (P<0.05) in treated cells. We subsequently co-cultured the apoptotic cardiomyocytes with BMCs and assessed cell fusion by flow cytometry. Fusion was rare in the non-treated control cardiomyocytes (0.3%), while H(2) O(2) treatment led to significantly higher fusion rates than the control group (P<0.05), with the highest rate of 7.9±0.3% occurring at 25 μM H(2) O(2) . We found an inverse correlation between cell fusion and completion of cardiomyocyte apoptosis (R(2) =0.9863). An in vivo mouse model provided evidence of cell fusion in the infarcted myocardium following the injection of BMCs. The percentage of cells undergoing fusion was significantly higher in mice injected with BMCs following infarction (8.8±1.3%) compared to mice that did not undergo infarction (4.6±0.6%, P<0.05). Enhancing cell fusion may be one method to preserve cardiomyocytes following myocardial infarction, and this new approach may provide a novel target for cardiac regenerative therapies. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Wei-Jian Yang; Shu-Hong Li; Richard D Weisel; Shi-Ming Liu; Ren-Ke Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-16
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  -     ISSN:  1582-4934     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Department of Cardiology, Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, China; Division of Cardiovascular Surgery and Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
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