TY - JOUR
T1 - Application of mesenchymal stem cell-derived cardiomyocytes as bio-pacemakers
T2 - Current status and problems to be solved
AU - Tomita, Yuichi
AU - Makino, Shinji
AU - Hakuno, Daihiko
AU - Hattan, Naoichiro
AU - Kimura, Kensuke
AU - Miyoshi, Shunichiro
AU - Murata, Mitsushige
AU - Ieda, Masaki
AU - Fukuda, Keiichi
N1 - Funding Information:
Acknowledgments This study was supported by the program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation (NIBIO), Japan, and research grants from the Ministry of Education, Science and Culture, Japan.
PY - 2007/2
Y1 - 2007/2
N2 - 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 IK1 and IKr were expressed before differentiation. After differentiation, ion channels underlying ICa,L and If were expressed first, followed by ion channels mediating Ito and IK,ATP. Differentiated CMG cells expressed β-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.
AB - 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 IK1 and IKr were expressed before differentiation. After differentiation, ion channels underlying ICa,L and If were expressed first, followed by ion channels mediating Ito and IK,ATP. Differentiated CMG cells expressed β-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.
KW - Bone marrow
KW - Cardiomyocyte
KW - Mesenchymal stem cell
KW - Pacemaker
KW - Transplantation
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U2 - 10.1007/s11517-007-0163-4
DO - 10.1007/s11517-007-0163-4
M3 - Article
C2 - 17262204
AN - SCOPUS:33847167064
SN - 0140-0118
VL - 45
SP - 209
EP - 220
JO - Medical and Biological Engineering and Computing
JF - Medical and Biological Engineering and Computing
IS - 2
ER -