Application of mesenchymal stem cells for the regeneration of cardiomyocyte and its use for cell transplantation therapy.
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 alpha1A, alpha1B, alpha1D, beta1, and beta2 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 (beta1-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.
Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo, Japan. kfukuda@sc.itc.keio.ac.jp
Keiichi
K
Fukuda
D000200:Action Potentials; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002469:Cell Separation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003285:Contractile Proteins / Q000378:metabolism; D006333:Heart Failure / Q000628:therapy; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D012038:Regeneration; D023822:Tissue Engineering
D003285:Contractile Proteins; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; D001374:Azacitidine