Document Detail

Cardiomyocytes can be generated from marrow stromal cells in vitro.
MedLine Citation:
PMID:  10074487     Owner:  NLM     Status:  MEDLINE    
We have isolated a cardiomyogenic cell line (CMG) from murine bone marrow stromal cells. Stromal cells were immortalized, treated with 5-azacytidine, and spontaneously beating cells were repeatedly screened. The cells showed a fibroblast-like morphology, but the morphology changed after 5-azacytidine treatment in approximately 30% of the cells; they connected with adjoining cells after one week, formed myotube-like structures, began spontaneously beating after two weeks, and beat synchronously after three weeks. They expressed atrial natriuretic peptide and brain natriuretic peptide and were stained with anti-myosin, anti-desmin, and anti-actinin antibodies. Electron microscopy revealed a cardiomyocyte-like ultrastructure, including typical sarcomeres, a centrally positioned nucleus, and atrial granules. These cells had several types of action potentials, such as sinus node-like and ventricular cell-like action potentials. All cells had a long action potential duration or plateau, a relatively shallow resting membrane potential, and a pacemaker-like late diastolic slow depolarization. Analysis of the isoform of contractile protein genes, such as myosin heavy chain, myosin light chain, and alpha-actin, indicated that their muscle phenotype was similar to that of fetal ventricular cardiomyocytes. These cells expressed Nkx2.5/Csx, GATA4, TEF-1, and MEF-2C mRNA before 5-azacytidine treatment and expressed MEF-2A and MEF-2D after treatment. This new cell line provides a powerful model for the study of cardiomyocyte differentiation.
S Makino; K Fukuda; S Miyoshi; F Konishi; H Kodama; J Pan; M Sano; T Takahashi; S Hori; H Abe; J Hata; A Umezawa; S Ogawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  103     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-03-31     Completed Date:  1999-03-31     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  697-705     Citation Subset:  AIM; IM    
Cardiopulmonary Division, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
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MeSH Terms
Action Potentials
Bone Marrow Cells / cytology*
Cell Differentiation
Cell Line*
Cell Lineage
Heart / physiology
Mice, Inbred C3H
Muscle Proteins / physiology
Myocardium / cytology*
Stromal Cells / cytology*
Reg. No./Substance:
0/Muscle Proteins

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