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Curr Pharm Biotechnol. 2019 Jun 28. doi: 10.2174/1389201020666190628143345. [Epub ahead of print]

Cardiotoxicity assessment of drugs using human iPS cell-derived cardiomyocytes: From proarrhythmia risk to cardiooncology.

Author information

1
Division of Pharmacology, National Institute of Health Sciences (NIHS), Kanagawa, 210-9501. Japan.

Abstract

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 proarrhythmia 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 proarrhythmic and contractile potentials. This review provides new insights into the practical application of hiPSC-CMs in early or late-stage non-clinical testing during drug development.

KEYWORDS:

cardiac safety; contractility; human iPS cells; multi-electrode array; proarrhythmia

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