Establishment of the method to evaluate cardiac toxicity by real-time cell analysis system on human embryonic stem cells / 中国药理学通报

ABSTRACT

Aim To establish an in vitro early drug cardiac tox-icity evaluation method by human embryonic stem cells derived cardiomyocytes ( hESC-CM) and real-time cell analysis Cardio (RTCA Cardio) system. Method The hESC-CM were cultured at RTCA Cardio E-Plate 96. Impedance signals from hESC-CM were analyzed for beating rate, contraction amplitude and beating rhythm irregularity to determine the optimum inoculation density and detection duration. Based on this, we used 0. 1 % DMSO to be the solvent and quinidine (0. 2, 0. 78, 3. 13, 12. 5, 50 and 100 μmol·L - 1 ) known as affecting cardiac activity to validate this method. Result The results revealed no significant changes in the cell index (CI), transient pulse patterns, beating rate and amplitude of hESC-CM. Quinidine will affect the CI and transi-ent pulse patterns of hESC-CM and decrease the beating rate and amplitude of hESC-CM when its concentration ≥3. 13 μmol · L - 1 . And this effect is concentration-dependent, the higher the concentration,the more time they need to recover beating and the more significant the beating rate and amplitude inhibition of quinidine on hESC-CM. Conclusion The method established by hESC-CM and RTCA Cardio system can detect the effect of quinidine on the contraction of hESC-CM, and this indicates that this method has the potential to be an attractive high-throughput tool for screening potential drugs in early evaluation of drug car-diotoxicity.