Yokoo Noritaka, Baba Shiro, Kaichi Shinji, Niwa Akira, Mima Takahiro, Doi Hiraku, Yamanaka Shinya, Nakahata Tatsutoshi, Heike Toshio
Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
Biochem Biophys Res Commun. 2009 Sep 25;387(3):482-8. doi: 10.1016/j.bbrc.2009.07.052. Epub 2009 Jul 16.
Developing effective drug therapies for arrhythmic diseases is hampered by the fact that the same drug can work well in some individuals but not in others. Human induced pluripotent stem (iPS) cells have been vetted as useful tools for drug screening. However, cardioactive drugs have not been shown to have the same effects on iPS cell-derived human cardiomyocytes as on embryonic stem (ES) cell-derived cardiomyocytes or human cardiomyocytes in a clinical setting. Here we show that current cardioactive drugs affect the beating frequency and contractility of iPS cell-derived cardiomyocytes in much the same way as they do ES cell-derived cardiomyocytes, and the results were compatible with empirical results in the clinic. Thus, human iPS cells could become an attractive tool to investigate the effects of cardioactive drugs at the individual level and to screen for individually tailored drugs against cardiac arrhythmic diseases.
开发用于治疗心律失常疾病的有效药物疗法受到这样一个事实的阻碍,即同一种药物在某些个体中效果良好,但在其他个体中却不然。人类诱导多能干细胞(iPS细胞)已被视为药物筛选的有用工具。然而,在临床环境中,心脏活性药物对iPS细胞衍生的人类心肌细胞的作用尚未显示出与对胚胎干细胞(ES细胞)衍生的心肌细胞或人类心肌细胞的作用相同。在这里,我们表明,目前的心脏活性药物对iPS细胞衍生的心肌细胞的搏动频率和收缩性的影响与对ES细胞衍生的心肌细胞的影响大致相同,并且结果与临床经验结果相符。因此,人类iPS细胞可能成为一个有吸引力的工具,用于在个体水平上研究心脏活性药物的作用,并筛选针对心律失常疾病的个性化定制药物。