Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells

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• 作者：Peishi Yan ; Atsushi Nagasawa ; Hideki Uosaki ; Akihiro Sugimoto ; Kohei Yamamizu ; Mizue Teranishi ; Hiroyuki Matsuda ; Satoshi Matsuoka ; Tadashi Ikeda ; Masashi Komeda ; Ryuzo Sakata ; Jun K. Yamashita
• 关键词：Cyclosporin-A ; Cardiac progenitor ; Cardiomyocytes ; Differentiation ; Embryonic stem cells
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：30 January 2009
• 年：2009
• 卷：379
• 期：1
• 页码：115-120
• 全文大小：2538 K

文摘

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.