In Vitro Models

Assessing arrhythmogenic risk in in vitro models of cardiac tissue

Utilizing a human iPSC-cardiomyocyte 3D microtissue platform, we assess dose sensitivity of environmental toxicants and pharmaceuticals for arrhythmic events by evaluating voltage and calcium handling via optical mapping in collaboration with Drs. Bum-Rak Choi and Ulrike Mende (RI Hospital).  Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we have shown that our microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range (Kofron et al 2021). We continue to validate our model with known toxicants over large concentration ranges, and with collaborators at ScitoVation, Inc, we are developing in vitro to in vivo extrapolation (IVIVE) and other models to maximize the risk assessment capabilities of our platform.

Atrial Arrhythmias