Yan Peishi, Nagasawa Atsushi, Uosaki Hideki, Sugimoto Akihiro, Yamamizu Kohei, Teranishi Mizue, Matsuda Hiroyuki, Matsuoka Satoshi, Ikeda Tadashi, Komeda Masashi, Sakata Ryuzo, Yamashita Jun K
Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Biochem Biophys Res Commun. 2009 Jan 30;379(1):115-20. doi: 10.1016/j.bbrc.2008.12.019. Epub 2008 Dec 16.
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.
虽然心脏祖细胞应该是心脏再生的合适材料，但尚未建立从胚胎干细胞（ES细胞）诱导心脏祖细胞的有效方法。在扩展我们系统的ES细胞心血管分化方法的过程中，我们在此展示了从ES细胞高效且特异性地扩增心肌细胞和高心脏源性祖细胞的方法。一种免疫抑制剂环孢菌素A（CSA）显示出一种新的作用，它特异性地作用于中胚层细胞，使心脏祖细胞以及心肌细胞大幅增加10至20倍。使用这种方法，从一个小鼠ES细胞大约可以诱导出200个心肌细胞。在将扩增的祖细胞移植到大鼠心肌梗死模型后，它们成功地作为心肌细胞整合到梗死心脏的瘢痕组织中。CSA以一种新的中胚层特异性、不依赖NFAT的方式引发了从中胚层对心脏谱系的特异性诱导。这种简单而有效的分化技术将扩展到诱导多能干细胞（iPS细胞），并广泛地促进心脏再生。
