Reprogramming of bone marrow mesenchymal stem cells into cardiomyocytes

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Abstract

We have isolated a cardiomyogenic cell line (CMG cell) from murine bone marrow mesenchymal stem cells. The cells showed a fibroblast-like morphology, but the morphology changed after 5-azacytidine exposure. They began spontaneous beating after 2 weeks, and expressed ANP and BNP. Electron microscopy revealed a cardiomyocyte-like ultrastructure. These cells had several types of action potentials: sinus-node-like and ventricular-cell-like action potentials. The isoform of contractile protein genes indicated that their muscle phenotype was similar to fetal ventricular cardiomyocytes. They expressed α1A, α1B, β1, β1, and P2 adrenergic and M1 and M2 adrenergic and M1 and M2 muscarinic receptors. Stimulation with phenylephrine, isoproterenol and carbachol increased ERK phosphorylation and second messengers. Isoproterenol increased the beating rate, which was blocked with CGP20712A (β1, -selective blocker). These findings indicated that cell transplantation therapy for the patients with heart failure might possibly be achieved using the regenerated cardiomyocytes from autologous bone marrow cells in the near future.

Original languageEnglish
Pages (from-to)1027-1038
Number of pages12
JournalComptes Rendus - Biologies
Volume325
Issue number10
DOIs
Publication statusPublished - 2002 Oct 1

Keywords

  • Adrenergic receptor
  • Bone marrow stroma
  • Cardiomyocyte
  • Differentiation
  • Mesenchymal stem cell
  • Muscarinic receptor
  • Regenerative medicine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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