Improvement of human iPSC-derived cardiomyocyte treated with subchronic electrical stimulation for evaluating the cardiotox risk

Abstract

Cardiotoxicity, such as arrhythmia, unexpected chrono- or inotropic effects, has been one of the most critical reasons for a termination of drug development. Consortium for Safety Assessment using Human iPS cells (CSAHi) aims to clarify the usefulness of human iPS cell-derived cardiomyocytes (iPS-CMs) in drug safety evaluation. Previously, we have demonstrated that the iPS cell-derived cardiomyocytes with several assay systems could be the powerful tools for detecting these risks. However, it is also known that the predictive accuracy is not fully enough due to immaturity of iPSC derived cells. In this study, we tested the improvement of the evaluating system using the electrically-stimulated iPSC-CMs, which have functionally mature phenotypes.