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Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells.

Publication ,  Journal Article
Shadrin, IY; Yoon, W; Li, L; Shepherd, N; Bursac, N
Published in: Scientific reports
July 2015

Cardiac cell therapies involving bone marrow-derived human mesenchymal stem cells (hMSCs) have shown promising results, although their mechanisms of action are still poorly understood. Here, we investigated direct interactions between hMSCs and cardiomyocytes in vitro. Using a genetic Ca(2+) indicator gCaMP3 to efficiently label hMSCs in co-cultures with neonatal rat ventricular myocytes (NRVMs), we determined that 25-40% of hMSCs (from 4 independent donors) acquired periodic Ca(2+) transients and cardiac markers through spontaneous fusion with NRVMs. Sharp electrode and voltage-clamp recordings in fused cells showed action potential properties and Ca(2+) current amplitudes in between those of non-fused hMSCs and NRVMs. Time-lapse video-microscopy revealed the first direct evidence of active fusion between hMSCs and NRVMs within several hours of co-culture. Application of blebbistatin, nifedipine or verapamil caused complete and reversible inhibition of fusion, suggesting potential roles for actomyosin bridging and Ca(2+) channels in the fusion process. Immunostaining for Cx43, Ki67, and sarcomeric α-actinin showed that fused cells remain strongly coupled to surrounding NRVMs, but downregulate sarcomeric structures over time, acquiring a non-proliferative and non-contractile phenotype. Overall, these results describe the phenotype and mechanisms of hybrid cell formation via fusion of hMSCs and cardiomyocytes with potential implications for cardiac cell therapy.

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Published In

Scientific reports

DOI

EISSN

2045-2322

ISSN

2045-2322

Publication Date

July 2015

Volume

5

Start / End Page

12043

Related Subject Headings

  • Troponin T
  • Time-Lapse Imaging
  • Real-Time Polymerase Chain Reaction
  • Rats, Sprague-Dawley
  • Rats
  • Myosin Type II
  • Myocytes, Cardiac
  • Microscopy, Video
  • Mesenchymal Stem Cells
  • Ions
 

Citation

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Shadrin, I. Y., Yoon, W., Li, L., Shepherd, N., & Bursac, N. (2015). Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells. Scientific Reports, 5, 12043. https://doi.org/10.1038/srep12043
Shadrin, Ilya Y., Woohyun Yoon, Liqing Li, Neal Shepherd, and Nenad Bursac. “Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells.Scientific Reports 5 (July 2015): 12043. https://doi.org/10.1038/srep12043.
Shadrin IY, Yoon W, Li L, Shepherd N, Bursac N. Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells. Scientific reports. 2015 Jul;5:12043.
Shadrin, Ilya Y., et al. “Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells.Scientific Reports, vol. 5, July 2015, p. 12043. Epmc, doi:10.1038/srep12043.
Shadrin IY, Yoon W, Li L, Shepherd N, Bursac N. Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells. Scientific reports. 2015 Jul;5:12043.

Published In

Scientific reports

DOI

EISSN

2045-2322

ISSN

2045-2322

Publication Date

July 2015

Volume

5

Start / End Page

12043

Related Subject Headings

  • Troponin T
  • Time-Lapse Imaging
  • Real-Time Polymerase Chain Reaction
  • Rats, Sprague-Dawley
  • Rats
  • Myosin Type II
  • Myocytes, Cardiac
  • Microscopy, Video
  • Mesenchymal Stem Cells
  • Ions