Shinozawa Tadahiro, Tsuji Akiko, Imahashi Kenichi, Nakashima Kosuke, Sawada Hiroshi, Toyoshiba Hiroyoshi, Yamamoto Satoshi, Takami Kenji, Imai Ryoetsu
Development Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan.
J Biomol Screen. 2009 Mar;14(3):239-45. doi: 10.1177/1087057108330112. Epub 2009 Feb 11.
Although embryonic stem cell (ESC)-derived cardiomyocytes may be a powerful tool in drug discovery, their potential has not yet been fully explored. Nor has a detailed comparison with adult heart tissue been performed. We have developed a method for efficient production of cardiomyocyte-rich embryoid bodies (EBs) from murine ESCs. Analysis of global gene expression profiles showed that EBs on day 7 and/or 21 of differentiation (d7CMs and d21CMs, respectively) were similar to adult heart tissue for genes categorized as regulators of muscle contraction or voltage-gated ion channel activity, although d21CMs were more mature than d7CMs for contractile components related to morphological structures. Calcium and sodium channel blockers altered Ca2+ transients, and isoproterenol, a beta-adrenergic compound, increased the rate of beating in d7CMs and d21CMs. Our gene analytic system therefore enabled us to identify genes that are expressed in the physiological pathways associated with ion channels and structural components in d7CMs and d21CMs. We conclude that EBs might be of use for the basic screening of drugs that might affect contractile function through ion channels.
尽管胚胎干细胞（ESC）来源的心肌细胞可能是药物研发中的有力工具，但其潜力尚未得到充分探索。与成年心脏组织的详细比较也尚未进行。我们已经开发出一种从鼠胚胎干细胞高效生产富含心肌细胞的胚状体（EBs）的方法。对整体基因表达谱的分析表明，分化第7天和/或第21天的EBs（分别为d7CMs和d21CMs）在归类为肌肉收缩或电压门控离子通道活性调节因子的基因方面与成年心脏组织相似，尽管在与形态结构相关的收缩成分方面，d21CMs比d7CMs更成熟。钙通道阻滞剂和钠通道阻滞剂改变了Ca2+瞬变，而β-肾上腺素能化合物异丙肾上腺素增加了d7CMs和d21CMs的跳动速率。因此，我们的基因分析系统使我们能够鉴定出在d7CMs和d21CMs中与离子通道和结构成分相关的生理途径中表达的基因。我们得出结论，EBs可能可用于对可能通过离子通道影响收缩功能的药物进行基础筛选。
