Points to consider for a validation study of iPS cell-derived cardiomyocytes using a multi-electrode array system

Abstract

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.