Growing evidence suggests that Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
(hiPSC-CMs) can be used as a new human cell-based platform to assess cardiac toxicity/safety
during drug development. Cardiotoxicity assessment is highly challenging due to species differences
and various toxicities, such as electrophysiological and contractile toxicities, which can result in
proarrhythmia and heart failure. To explore proarrhythmic risk, the Multi-Electrode Array (MEA) platform
is widely used to assess QT-interval prolongation and the proarrhythmic potential of drug candidates
using hiPSC-CMs. Several consortiums, including the Comprehensive in vitro Proarrhythmia
Assay (CiPA) and the Japanese iPS Cardiac Safety Assessment (JiCSA), have demonstrated the applicability
of hiPSC-CMs/MEA for assessing the torsadogenic potential of drug candidates. Additionally,
contractility is a key safety issue in drug development, and efforts have been undertaken to measure
contractility by a variety of imaging-based methods using iPS-CMs. Therefore, hiPSC-CMs might
represent a standard testing tool for evaluating the proarrhythmic and contractile potentials. This review
provides new insights into the practical application of hiPSC-CMs in early or late-stage nonclinical
testing during drug development.
Keywords: Cardiac safety, human iPS cells, multi-electrode array, proarrhythmia, contractility, standardization.
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