A mathematical model of hiPSC cardiomyocytes electromechanics

We present the first hiPSC-CM computational model that accounts for essential AP, CaT, and mechanical biomarkers incorporating experimental variability. The introduced passive force handling enables the model to capture the inotropic effect of non-cardiomyocytes in hiPSC-CM tissues. Simulated cell shortening and contraction –relaxation indices fall within experimental ranges, and EAD-based aftercontractions predicted by the model are in accord with experimental observations. Predicted Verapamil and Bay-K 8644 inotropic effects agree with in vitro data. AbstractHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are becoming instrumental in cardiac research, human-based cell level cardiotoxicity tests, and developing patient-specific care. As one of the principal functional readouts is contractility, we propose a novel electromechanical hiPSC-CM computational model named the hiPSC-CM-CE. This model comprises a reparametrized version of contractile element (CE) by Rice et al., 2008, with a new passive force formulation, integrated into a hiPSC-CM electrophysiology formalism by Paci et al. in 2020. Our simulated results were validated againstin vitro data reported for hiPSC-CMs at matching conditions from different labs. Specifically, key action potential (AP) and calcium transient (CaT) biomarkers simulated by the hiPSC-CM-CE model were within the experimental ranges. On the mechanical side, simulated cell shortening, contraction –relaxation kinetic indic...
Source: Physiological Reports - Category: Physiology Authors: Tags: ORIGINAL ARTICLE Source Type: research