Development of mature cardiomyocytes from human iPS cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293056
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Kanda Yasunari 国立医薬品食品衛生研究所, 薬理部, 室長 (70510387)
• Co-Investigator(Kenkyū-buntansha): 大島 英揮 名古屋大学, 医学部附属病院, 講師 (40378188)
• Co-Investigator(Renkei-kenkyūsha): Kurokawa Junko 静岡県立大学, 薬学部, 教授 (40396982)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: iPS細胞 / 心筋細胞 / 成熟化 / インシリコ / イオンチャネル / 安全性薬理

Outline of Final Research Achievements

Drug-induced cardiac arrhythmias have been a major reason for drug withdrawal at late stage of clinical trials. Human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) are expected to be applicable to cardiac drug safety testing as research tools. In the present study, our patch-clamp recordings and imaging with voltage-sensitive dye revealed that iPS-CMs exhibited relatively depolarized maximum diastolic potential and lower conduction velocity, suggesting an immature differentiation state of the iPS-CMs. We next established our mathematical simulation in iPS-CMs and found that low expression of the inward-rectifier potassium (IK1) channel is a determinant of spontaneous activity. We also fond that transduction of KCNJ2, which encodes the IK1 channel, induced electrophysiological maturation of iPS-CMs. Thus, our novel approach would provide new insights into the evaluation of drug-induced caridiac toxicities in iPS-CMs.

Free Research Field

薬理学、幹細胞生物学、