Simulated micro-electrode array recordings from stem cell-derived cardiomyocytes

Abstract

Human stem cell-derived cardiomyocytes (hSC-CMs) are a promising medium for cardiovascular safety assessment. The effects of pharmaceutical compounds on the electrophysiological properties of these cells can be examined using micro-electrode arrays. Biomarkers derived from the recorded field potential give an indication of the effect of the compound on the tissue, and can therefore be used to make an initial judgement of the arrhythmic risk associated with a compound.<br><br>We propose a pipeline that combines ion channel screening data, micro-electrode array recordings and simulations to understand the mechanistic effects of a compound on the electrical activity recorded in an hSC-CM monolayer. A two-dimensional system is used to model the monolayer, from which simulated field potentials and biomarkers can be extracted. Despite previous work on modelling the distinct electrophysiology of hSC-CMs, there have been few tissue simulations to date. This process is more challenging than would be expected due to the spontaneous activity of the hSC-CMs and the presence of multiple cellular phenotypes. <br><br>There are several ways of representing the atrial-like and ventricular-like hSC-CMs within the monolayer; here we consider discrete areas of each phenotype. We investigate the predicted micro-electrode array recordings with the addition of a compound by using IC50 data from ion channel screens to modulate the ionic currents in the mathematical model. <br