Abstract 18892: Variations of Drug Responses in Induced Pluripotent Stem Cell-Derived Cardiomyocytes From Healthy Japanese Volunteers
Introduction: Cardiac safety assessment is an important process during drug discovery in order to prevent retractions of the new drugs from the market. Cardiac safety assessment using human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) are expected to replace some of the current method to assess cardiac safety, however, whether cardiac safety assessment using the iPS-CMs from single clone/donor truly predict the cardiac risk for general population remains unknown. Here, we investigated the basal characters and drug responses of iPS-CMs from several Japanese volunteers and assessed the presence of clone-to-clone and donor-to-donor differences.
Methods and Results: iPSCs were established from healthy Japanese those do not have any familial or past history of heart diseases. 12-lead electrocardiogram was examined to ensure no signs of genetic heart diseases. Cardiac differentiation was performed by sequential treatment with Wnt signaling agonists and antagonists. Variations between iPS-CMs were analyzed by using FDSS/uCELL. Unexpectedly, there were no significant clone-to-clone and donor-to-donor differences in basal characters and in responses to various drugs. There were clone-to-clone difference in the type of arrhythmic events that appears by arrhythmogenic drugs, but the minimal concentrations that induce arrhythmic events were within the ratio of 3 in all the drugs tested.
Conclusions: Our study demonstrated that hiPS-CMs exhibit highly reproducible characters and responses against multiple drugs, irrespective to the difference of clone and donor from which it was derived, as long as the donor is healthy and the cardiomyocytes are produced properly.Figure; Representative images of the effect of multiple drugs on calcium transient of hiPS-CM.
Author Disclosures: M. Ito: None. I. Komuro: None. A. Naito: None.
- © 2016 by American Heart Association, Inc.