title: Application of mesenchymal stem cell-derived cardiomyocytes as bio-pacemakers: current status and problems to be solved.
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 I(K1) and I(Kr) were expressed before differentiation. After differentiation, ion channels underlying ICa,L and If were expressed first, followed by ion channels mediating I(to) and I(K,ATP). Differentiated CMG cells expressed beta-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.
authors.affiliation: Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Institute of Integrated Medical Research, 35 Shinanomachi, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tomita
authors.forename: Shinji
authors.initials: S
authors.lastname: Makino
authors.forename: Daihiko
authors.initials: D
authors.lastname: Hakuno
authors.forename: Naoichiro
authors.initials: N
authors.lastname: Hattan
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kimura
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Miyoshi
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Murata
authors.forename: Masaki
authors.initials: M
authors.lastname: Ieda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000473:pathology / Q000628:therapy*; D002450:Cell Communication; D006329:Heart Conduction System / Q000502:physiology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000502:physiology*