Advanced Cardiovascular Toxicity Screening: Integrating Human iPSC-Derived Cardiomyocytes with In Silico Models

Abstract

The pharmaceutical industry is evolving with the use of hiPSC-derived cardiomyocytes (hiPSC-CM) for in vitro cardiac safety screening. Traditional reliance on QT interval prolongation as a main cardiotoxicity marker is being challenged. In addition, Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative recommends using computer modeling and in silico platforms as more comprehensive approach for cardiotoxicity testing in conjunction with hiPSC-CM in vitro screening. Our study presents such an innovative platform that integrates in vitro hiPSC-CM propagation test with in silico models to assess cardiotoxicity. Utilizing the electrophysiological and morphological characteristics of hiPSC-CM, we offer a thorough evaluation of potential drug-induced cardiac risks by computer modelling. We show, using the example of lidocaine and other antiarrhythmics, that using a integrative experimental and computer platform, the possibility to correctly display the clinical manifestations of side effects in advance.