• Open Access

Cell fusion contributes to the rescue of apoptotic cardiomyocytes by bone marrow cells

Authors

  • Wei-Jian Yang,

    1. Department of Cardiology, Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, China
    2. Division of Cardiovascular Surgery and Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
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    • These authors contributed equally to this work.
  • Shu-Hong Li,

    1. Division of Cardiovascular Surgery and Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
    2. Department of Surgery, Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada
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    • These authors contributed equally to this work.
  • Richard D. Weisel,

    1. Division of Cardiovascular Surgery and Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
    2. Department of Surgery, Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada
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  • Shi-Ming Liu,

    1. Department of Cardiology, Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, China
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  • Ren-Ke Li

    Corresponding author
    1. Division of Cardiovascular Surgery and Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
    2. Department of Surgery, Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada
    • Department of Cardiology, Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, China
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Correspondence to: Ren-Ke LI, MD, PhD, Toronto General Research Institute, MaRS Centre, Toronto Medical Discovery Tower, 101 College St., Room 3-702, Toronto, ON, Canada, M5G 1L7.

Tel.: +416-581-7492

Fax: +416-581-7493

E-mail: renkeli@uhnresearch.ca

Abstract

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-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 (H2O2). The TUNEL assay demonstrated an increase in apoptosis from 4.5 ± 1.3% in non-treated cells to 19.0 ± 4.4% (< 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 H2O2 treatment led to significantly higher fusion rates than the control group (< 0.05), with the highest rate of 7.9 ± 0.3% occurring at 25 μM H2O2. We found an inverse correlation between cell fusion and completion of cardiomyocyte apoptosis (R2 = 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%, < 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.

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