Kanda Yasunari, Yamazaki Daiju, Kurokawa Junko, Inutsuka Takashi, Sekino Yuko
Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Japan iPS Cardiac Safety Assessment (JiCSA).
Japan iPS Cardiac Safety Assessment (JiCSA); Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
J Pharmacol Toxicol Methods. 2016 Sep-Oct;81:196-200. doi: 10.1016/j.vascn.2016.06.007. Epub 2016 Jun 29.
Human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) provide a novel assay system to assess cardiac safety in drug development to overcome a problem of species difference in non-clinical testing during drug development. Using the multi-electrode array (MEA) platform, electrophysiological activities of iPS-CMs can be recorded easily to assess QT prolongation and proarrhythmic potential of drug candidates. Here we have established a standardized protocol to evaluate the possibility of iPS-CMs, and shared the protocol with an international consortium. To obtain reproducible and reliable experimental data from these cells, we determined the optimal experimental conditions, such as cell density, MEA coating, culture conditions, high-pass filter frequency, definition of early afterdepolarization or triggered activity, and calibration compounds. Based on the protocol, our validation study using 60 compounds is in progress. Thus, MEA-based experiments using iPS-CMs would be a standard testing method to evaluate QT prolongation and proarrhythmic potentials.
人诱导多能干细胞衍生的心肌细胞（iPS-CMs）为药物开发中的心脏安全性评估提供了一种新的检测系统，以克服药物开发过程中非临床测试中物种差异的问题。使用多电极阵列（MEA）平台，可以轻松记录iPS-CMs的电生理活动，以评估候选药物的QT间期延长和促心律失常潜力。在此，我们建立了一个标准化方案来评估iPS-CMs的可能性，并与一个国际联盟共享了该方案。为了从这些细胞中获得可重复和可靠的实验数据，我们确定了最佳实验条件，如细胞密度、MEA涂层、培养条件、高通滤波器频率、早期后去极化或触发活动的定义以及校准化合物。基于该方案，我们使用60种化合物的验证研究正在进行中。因此，基于MEA的iPS-CMs实验将成为评估QT间期延长和促心律失常潜力的标准测试方法。
