日本一个研究小组日前宣布，他们开发出了利用诱导多功能干细胞（iPS细胞）高效培养心肌细胞的方法，今后如果能够利用这一方法大量培养心肌细胞，将可用于恢复因心肌梗塞而受损的心脏功能。

京都大学iPS细胞研究所副教授山下润率领的研究小组，向实验鼠的iPS细胞加入环孢菌素A（一种免疫抑制剂）后进行培养，发现发育成的心肌细胞数量是不加入环孢菌素A时的约12倍。而利用人类iPS细胞进行培养时，在培养到第12天的时候，确认生成的心肌细胞数量，是不加入环孢菌素A时的4倍以上。

研究小组认为，这表明环孢菌素A在诱导实验鼠和人类iPS细胞发育成心肌细胞过程中发挥了重要作用。

研究小组确认，利用人类iPS细胞培养的心肌细胞与人类心脏心室细胞拥有同样的性质和结构。相关论文已刊登在新一期美国科学杂志《公共科学图书馆·综合》网络版上。

原文出处：

PLoS ONE 6(2): e16734. doi:10.1371/journal.pone.0016734

Induction and Enhancement of Cardiac Cell Differentiation from Mouse and Human Induced Pluripotent Stem Cells with Cyclosporin-A

Masataka Fujiwara1,2, Peishi Yan1,3¤, Tomomi G. Otsuji4,5, Genta Narazaki1,6, Hideki Uosaki1,6, Hiroyuki Fukushima1,6, Koichiro Kuwahara2, Masaki Harada2, Hiroyuki Matsuda7, Satoshi Matsuoka7, Keisuke Okita8, Kazutoshi Takahashi8, Masato Nakagawa8, Tadashi Ikeda3, Ryuzo Sakata3, Christine L. Mummery9, Norio Nakatsuji10,11, Shinya Yamanaka8,12, Kazuwa Nakao2, Jun K. Yamashita1,6*

Induced pluripotent stem cells (iPSCs) are novel stem cells derived from adult mouse and human tissues by reprogramming. Elucidation of mechanisms and exploration of efficient methods for their differentiation to functional cardiomyocytes are essential for developing cardiac cell models and future regenerative therapies. We previously established a novel mouse embryonic stem cell (ESC) and iPSC differentiation system in which cardiovascular cells can be systematically induced from Flk1+ common progenitor cells, and identified highly cardiogenic progenitors as Flk1+/CXCR4+/VE-cadherin? (FCV) cells. We have also reported that cyclosporin-A (CSA) drastically increases FCV progenitor and cardiomyocyte induction from mouse ESCs. Here, we combined these technologies and extended them to mouse and human iPSCs. Co-culture of purified mouse iPSC-derived Flk1+ cells with OP9 stroma cells induced cardiomyocyte differentiation whilst addition of CSA to Flk1+ cells dramatically increased both cardiomyocyte and FCV progenitor cell differentiation. Spontaneously beating colonies were obtained from human iPSCs by co-culture with END-2 visceral endoderm-like cells. Appearance of beating colonies from human iPSCs was increased approximately 4.3 times by addition of CSA at mesoderm stage. CSA-expanded human iPSC-derived cardiomyocytes showed various cardiac marker expressions, synchronized calcium transients, cardiomyocyte-like action potentials, pharmacological reactions, and ultra-structural features as cardiomyocytes. These results provide a technological basis to obtain functional cardiomyocytes from iPSCs.