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

Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells
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DOI:
10.1016/j.bbrc.2008.12.019
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发表时间:
2009-01-30
影响因子:
3.1
通讯作者:
Yamashita, Jun K.
Yamashita, Jun K.
中科院分区:
生物学4区
文献类型:
--
作者:
Yan, Peishi;Nagasawa, Atsushi;Yamashita, Jun K.

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虽然心脏祖细胞应该是心脏再生的合适材料,但从胚胎斯坦细胞诱导心脏祖细胞的有效方法尚未建立。扩展了我们系统的胚胎干细胞心血管分化方法,在这里我们展示了从胚胎干细胞中高效和特异性地扩增心肌细胞和高度心源性祖细胞。一种免疫抑制剂环孢素A (cyclosporin A, CSA)显示出一种特异性作用于中胚层细胞的新效应,可使心脏祖细胞和心肌细胞的数量急剧增加10-20倍。使用这种方法,一个小鼠胚胎干细胞可以诱导出大约200个心肌细胞。细胞移植大鼠心肌梗死模型后,扩增祖细胞成功融入梗死心脏瘢痕组织作为心肌细胞。CSA以一种新颖的中胚层特异性、不依赖于NFAT的方式从中胚层诱导特异性心脏谱系。这种简单而有效的分化技术将扩展到诱导多能斯坦细胞(iPS),并广泛地促进心脏再生。(C) 2008爱思唯尔公司版权所有。
Though cardiac progenitor cells should be a suitable material for cardiac regeneration, efficient ways to induce cardiac progenitors from embryonic stein (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 stein (iPS) cells and broadly contribute to cardiac regeneration. (C) 2008 Elsevier Inc. All rights reserved.