2016 Volume 6 Issue 3 Pages 367-374
It is important to overcome a problem of species difference in non-clinical testing during drug development. Human induced pluripotent stem (iPS) cells are expected to resolve the problem. Recently, application of iPS cell-derived cardiomyocytes (iPS-CMs) has been focused on a novel assay system for safety pharmacology. We have prepared a common protocol using iPS-CMs and multi electrode array (MEA) system. From our results of prevalidation study, we organized a nation-wide consortium Japan iPS Cardiac Safety Assessment (JiCSA), for large-scale validation study. JiCSA has improved a MEA-based protocol using iPS-CMs and is now evaluating the effects of 60 compounds using iCell (Cellular Dynamics International) and MED64 MEA system (alpha MED Scientific). In parallel with our prevalidation study, a new CiPA (Comprehensive in vitro Proarrhythmia Assay) paradigm has been proposed by the US Food and Drug Administration (FDA), Cardiac Safety Research Consortium, nonprofit ILSI-Health and Environmental Sciences Institute (HESI), and Safety Pharmacology Society (SPS) for the cardiac proarrhythmia safety. We have shared our protocol and pilot study data using several ion channel blockers with CiPA. Thus, we will collaborate toward establishment of new testing methods to assess the cardiac safety paradigm. This international collaboration will provide scientific basis for revision of ICH S7B guideline. In this review, we will summarize our activities for the development of the standardized protocol using iPS-CMs for safety assessment. This study was supported by grants from the Ministry of Health Labor and Welfare and Japan Agency for Medical Research and development.
