CiPA-qualified human iPSC-derived cardiomyocytes: A new frontier in toxicity testing by evaluating drug-induced...

Drug-induced arrhythmias remain a significant challenge in drug development, often leading to serious cardiovascular complications and the withdrawal of approved drugs from the market. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative aims to enhance cardiac safety assessment by leveraging human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). In this study, we evaluated the effects of 28 drugs on a well-characterized hiPSC-CMs (YBLiCardio, Yashraj Biotechnology Ltd., Mumbai, India) using Electric Field Potential (EFP) measurements. The CardioExcyte 96 system recorded extracellular signals from 96 wells, functioning similarly to microelectrode arrays. Each drug was tested at four concentrations, and the effects were analyzed based on dynamic changes in beat patterns, with QT prolongation assessed by measuring the interval between the sodium spike and T-wave. Our results demonstrated that YBLiCardio cells responded to all drugs in line with the findings from the HESI CiPA study. Notably, droperidol (173 %) and domperidone (182 %), originally classified as intermediate-risk compounds, were identified as high-risk in our model, consistent with previous findings by Nguyen et al. (2017). Additionally, YBLiCardio showed enhanced predictive accuracy for chlorpromazine. These findings highlight the potential of hiPSC-CMs for proarrhythmia risk assessment within the CiPA framework, complementing ion channel data and in silico modeling approaches. Overall, YBLiCardio provides a robust and physiologically relevant platform for predicting cardiotoxicity, supporting safer and more efficient pre-clinical drug discovery & development.