Both human embryonic stem cell-derived and induced pluripotent stem cell-derived cardiomyocytes successfully recapitulated the cardiotoxic effects of E-4031, quinidine, isoprenaline, and haloperidol.
BACKGROUND: Cardiotoxicity remains an important concern in drug discovery. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have become an attractive platform to evaluate cardiotoxicity. However, the consistency between human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in prediction of cardiotoxicity has yet to be elucidated. METHODS: Here we screened the toxicities of four representative drugs (E-4031, isoprenaline, quinidine, and haloperidol) using both hESC-CMs and hiPSC-CMs, combined with an impedance-based bioanalytical method. RESULTS: It showed that both hESC-CMs and hiPSC-CMs can recapitulate cardiotoxicity and identify the effects of well-characterized compounds. CONCLUSIONS: The combined platform of hPSC-CMs and an impedance-based bioanalytical method could improve preclinical cardiotoxicity screening, holding great potential for increasing drug development accuracy.
Zhao et al. (Thu,) conducted a other in Cardiotoxicity (in vitro). Cardiotoxic drugs (E-4031, quinidine, isoprenaline, haloperidol) vs. Baseline (pre-dose) values was evaluated on IC50/EC50 for Cell Index and beating properties. Both human embryonic stem cell-derived and induced pluripotent stem cell-derived cardiomyocytes successfully recapitulated the cardiotoxic effects of E-4031, quinidine, isoprenaline, and haloperidol.