Human ES- and Induced Pluripotent Stem-Derived Cardiomyocytes. A Comparative Electrophysiological Study

Abstract

Special attention is directed to the potential application of human induced pluripotent stem (iPS) cell-derived cardiomyocytes for cardiac safety pharmacology and toxicology with fewer legal and ethical issues. Supply of commercially available products enables many researchers to test the utility in their own systems. Although variations of electrophysiological properties have been reported among pluripotent cell lines by classifying cardiac subtypes into nodal, atrial and ventricular cells, most cells are spontaneously contracting, which makes difficult to be implicated in adult human hearts. Thus, we sought objective description on action potential (AP) parameters recorded from perforated patch-clamped iCell cardiomyocytes (iCell-CMs, AJ/CDI) by systematically comparing with those from human ES-derived cardiomyocytes (hES-CMs, Cellartis). Mean +/- SE values of APD50 in iCell-CMs (382 +/- 38 ms, n=36) were significantly longer than those in hES-CMs (278 +/- 28 ms n=64), while APD90 in iCell-CMs (1210 +/- 346 ms, n=36) tended to be longer than those in hES-CMs (776 +/- 136 ms n=64). As for APD90, despite of the large sample size, there was no statistical significance between iPS-CM and hES-CMs. Detailed analysis of the variation by Gaussian fitting revealed that marked differences in shapes of probability distribution between iPS-CMs and hES-CMs. Although further studies are necessary to know if the variation of AP parameters affect drug responses, our data provide important information for cardiac safety assessments.