There is a pressing need for predictive in vitro assays suitable for high-throughput screening (HTS) to detect cardioactive effects of compounds early in the drug discovery process. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes are a relevant in vitro model for this purpose.
We have developed fully functional iPSC-derived ventricular cardiomyocytes that exhibit a relatively high level of maturity. This was demonstrated by an increased contraction profile, ultra-structural sarcomere organization, as well as improved electrophysiological properties. To assess their potential for application in HTS assays, we analyzed the effects of different cardioactive compounds on calcium transients and compared these data to well-established, medium-throughput multielectrode array (MEA)/impedance assays.
We conclude that our iPSC-derived cardiomyocytes combined with HTS-compatible assays form a highly relevant model to study pharmacological and toxicological responses of large numbers of drug candidates.