PMID- 22805279 OWN - NLM STAT- MEDLINE DCOM- 20140211 LR - 20211021 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 16 IP - 12 DP - 2012 Dec TI - Cell fusion contributes to the rescue of apoptotic cardiomyocytes by bone marrow cells. PG - 3085-95 LID - 10.1111/j.1582-4934.2012.01600.x [doi] AB - 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 ischaemia, 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 twofold when the cells were co-cultured with apoptotic (TNF-alpha 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 using flow cytometry. Fusion was rare in the non-treated control cardiomyocytes (0.3%), whereas 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 muM 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. CI - (c) 2012 The Authors Journal of Cellular and Molecular Medicine (c) 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. FAU - Yang, Wei-Jian AU - Yang WJ AD - Department of Cardiology, Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, China. FAU - Li, Shu-Hong AU - Li SH FAU - Weisel, Richard D AU - Weisel RD FAU - Liu, Shi-Ming AU - Liu SM FAU - Li, Ren-Ke AU - Li RK LA - eng GR - MOP102535/Canadian Institutes of Health Research/Canada GR - MOP86661/Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 147336-22-9 (Green Fluorescent Proteins) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Animals MH - Apoptosis MH - Bone Marrow Cells/*physiology MH - *Cell Fusion MH - Cells, Cultured MH - Coculture Techniques MH - Green Fluorescent Proteins MH - Heart Failure/*physiopathology MH - Hematopoietic Stem Cells/physiology MH - Hydrogen Peroxide/pharmacology MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/physiology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Myocardial Infarction/*physiopathology MH - Myocytes, Cardiac/*physiology MH - Oxidative Stress MH - Rats MH - Rats, Sprague-Dawley MH - Rats, Wistar PMC - PMC4393736 EDAT- 2012/07/19 06:00 MHDA- 2014/02/12 06:00 PMCR- 2012/12/01 CRDT- 2012/07/19 06:00 PHST- 2011/12/20 00:00 [received] PHST- 2012/07/09 00:00 [accepted] PHST- 2012/07/19 06:00 [entrez] PHST- 2012/07/19 06:00 [pubmed] PHST- 2014/02/12 06:00 [medline] PHST- 2012/12/01 00:00 [pmc-release] AID - 10.1111/j.1582-4934.2012.01600.x [doi] PST - ppublish SO - J Cell Mol Med. 2012 Dec;16(12):3085-95. doi: 10.1111/j.1582-4934.2012.01600.x.