Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineering

Research output: Contribution to journalArticle

232 Citations (Scopus)

Abstract

We have isolated a cardiomyogenic (CMG) cell line from murine bone marrow stroma. Stromal cells were immortalized, treated with 5-azacytidine, and spontaneous beating cells were repeatedly screened for. The cells showed a fibroblast-like morphology. However, this morphology changed after 5-azacytidine treatment in about 30% of the cells, which connected with adjoining cells after 1 week, formed myotube-like structures and began spontaneous beating after 2 weeks, and beat synchronously after 3 weeks. These cells expressed atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Electron microscopy revealed a cardiomyocyte-like ultrastructure including typical sarcomeres and atrial granules. They had sinus node-like or ventricular cell-like action potentials. Analysis of the isoform of contractile protein genes, such as myosin and α-actin, indicated that their phenotype was similar to fetal ventricular cardiomyocytes. These cells expressed Nkx2.5, GATA4, TEF-1, and MEF2-C mRNA before 5-azacytidine treatment, and expressed MEF2-A and MEF2-D after treatment. This new cell line provides a powerful model for the study of cardiomyocyte transplantation.

Original languageEnglish
Pages (from-to)187-193
Number of pages7
JournalArtificial Organs
Volume25
Issue number3
DOIs
Publication statusPublished - 2001

Fingerprint

Azacitidine
Tissue Engineering
Stem cells
Mesenchymal Stromal Cells
Tissue engineering
Cardiac Myocytes
Cells
Fibroblasts
Electron microscopy
Contractile Proteins
Brain
Bone
Genes
Brain Natriuretic Peptide
Atrial Natriuretic Factor
Myosins
Actins
Protein Isoforms
Messenger RNA
Cell Line

Keywords

  • 5-azacytidine
  • Bone marrow stroma
  • Cardiomyocyte
  • Differentiation
  • Mesenchymal stem cell

ASJC Scopus subject areas

  • Biophysics

Cite this

Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineering. / Fukuda, Keiichi.

In: Artificial Organs, Vol. 25, No. 3, 2001, p. 187-193.

Research output: Contribution to journalArticle

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