Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells |
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Authors: | Peishi Yan Atsushi Nagasawa Akihiro Sugimoto Mizue Teranishi Satoshi Matsuoka Masashi Komeda Jun K Yamashita |
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Institution: | a Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan b Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan c Department of Physiology and Biophysics, Kyoto University Graduate School of Medicine, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan d Nagoya Heart Center, Japan e Center for iPS Cell Research and Application, Institute for Integrated Cell-Material Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan |
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Abstract: | Though cardiac progenitor cells should be a suitable material for cardiac regeneration, efficient ways to induce cardiac progenitors from embryonic stem (ES) cells have not been established. Extending our systematic cardiovascular differentiation method of ES cells, here we show efficient and specific expansion of cardiomyocytes and highly cardiogenic progenitors from ES cells. An immunosuppressant, cyclosporin-A (CSA), showed a novel effect specifically acting on mesoderm cells to drastically increase cardiac progenitors as well as cardiomyocytes by 10-20 times. Approximately 200 cardiomyocytes could be induced from one mouse ES cell using this method. Expanded progenitors successfully integrated into scar tissue of infracted heart as cardiomyocytes after cell transplantation to rat myocardial infarction model. CSA elicited specific induction of cardiac lineage from mesoderm in a novel mesoderm-specific, NFAT independent fashion. This simple but efficient differentiation technology would be extended to induce pluripotent stem (iPS) cells and broadly contribute to cardiac regeneration. |
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Keywords: | Cyclosporin-A Cardiac progenitor Cardiomyocytes Differentiation Embryonic stem cells |
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