Toxicity testing in the era of induced pluripotent stem cells: A perspective regarding the use of patient-specific induced pluripotent stem cell-derived cardiomyocytes for cardiac safety evaluation

The development of human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has opened a new era to address the challenge of improving drug-induced cardiotoxicity prediction. Human iPSC-CMs can be generated from individuals with diverse genetic backgrounds and varying disease status, which provides unprecedented opportunities to assess drug-induced cardiotoxicity at the population level, ultimately, realizing personalized cardiac safety prediction and permitting mechanistic insights into genetic predisposition of drug-induced cardiotoxicity at the molecular and cellular levels. Reviewed herein are successful applications and limitations in using patient-specific iPSC-CMs for cardiac safety evaluation. Future directions for iPSC-CMs are also discussed. The aim of this review is to promote the further development of human iPSC-CM technology to address existing gaps in drug development, improve the prediction of patient susceptibility to therapeutic drugs, and enhance postmarketing surveillance of severe adverse drug reactions.