Failure to correctly predict adverse cardiotoxic effects of new pharmaceuticals is the major cause of com-pound attrition during drug development as well as for withdrawal of drugs already on the market. With recent advances in the stem cell field it is now possible to generate human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) that recapitulate the native behavior and accurately assess the pro-arrhythmic potentials of candidate drugs. At present, these cells are being actively investigated with high-throughput technology, especially through the CiPA initiative, for their potential use as a model system for complete cardiac safety screening. In our study, we adopted the current, CiPA-derived protocol as a “best practices” protocols and validated Cardiosight-S® hiPSC CM (NEXEL Co., Ltd, South Korea) accordingly.

We used automated patch clamp platforms and, in addition, combined impedance and MEA-like recordings were performed using the hybrid system CardioExcyte 96 to provide complementary data for patch clamp. Cardiosight-S® hiPSC-CM, reproducibly generated without genetic engineering or selection in a monolayer, are containing >95% cardiomyocytes (measured by cardiac troponin T positive cells). They displayed spontaneous beating and expressed the major cardiac markers and ion channels. Voltage-gated Na+, including the late component of the could be reliably recorded in those hiPSC-CM. ATX-II-activated INa, Late could be blocked by ranolazine with an efficacy in good agreement with the literature. Upon exposure to CiPA Phase II Validation Study Compounds identified as High, Medium or Low risk for manifesting hu-man TdP, the cells showed an expected ability to predict cardiotoxic effects. Expected prolongations or shortenings of the field potential duration or modified beating behaviours illustrate that the expected drug responses were reproduced with Cardiosight-S® Cardiomyocytes, suggesting high physiological relevance of the cells. The study confirms that the cells are suitable for use on high-throughput automated patch clamp devices and impedance/EFP platforms. First dataset on CiPA compounds derived from the cells are promising in a way that the cells own required properties in order to allow accurate drug safety testing.