Reprogramming of bone marrow mesenchymal stem cells into cardiomyocytes.
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 alpha 1A, alpha 1B, alpha 1D, beta 1, and beta 2 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 (beta 1-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.
Fukuda
Keiichi
K
Institute for Advanced Cardiac Therapeutics, Institute of Integrated Medical Research 7S1/7S2, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. kfukuda@sc.itc.keio.ac.jp
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006321:Heart / Q000196:embryology*; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008809:Mice, Inbred C3H; D032342:Muscle Cells / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*