Application of mesenchymal stem cell-derived cardiomyocytes as bio-pacemakers: Current status and problems to be solved

Yuichi Tomita, Shinji Makino, Daihiko Hakuno, Naoichiro Hattan, Kensuke Kimura, Shunichiro Miyoshi, Mitsushige Murata, Masaki Ieda, Keiichi Fukuda

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Bone marrow mesenchymal stem cells (CMG cells) are multipotent and can be induced by 5-azacytidine to differentiate into cardiomyocytes. We characterized the electrophysiological properties of these cardiomyocytes and investigated their potential for use as transplantable bio-pacemakers. After differentiation, action potentials in spontaneously beating cardiomyocytes were initially sinus node-like, but subsequently became ventricular cardiomyocyte-like. RT-PCR established that ion channels mediating IK1 and IKr were expressed before differentiation. After differentiation, ion channels underlying ICa,L and If were expressed first, followed by ion channels mediating Ito and IK,ATP. Differentiated CMG cells expressed β-adrenergic receptors and increased their beat rate in response to isoproterenol. CMG cardiomyocytes were purified using GFP fluorescence and transplanted into the free walls of the left ventricles of mice. The transplanted cardiomyocytes survived and connected to surrounding recipient cardiomyocytes via intercalated discs. Although further innovation is required, the present findings provide evidence of the potential for bone marrow-derived cardiomyocytes to be used as bio-pacemakers.

Original languageEnglish
Pages (from-to)209-220
Number of pages12
JournalMedical and Biological Engineering and Computing
Volume45
Issue number2
DOIs
Publication statusPublished - 2007 Feb 1

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Keywords

  • Bone marrow
  • Cardiomyocyte
  • Mesenchymal stem cell
  • Pacemaker
  • Transplantation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Computer Science Applications

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