In Silico Human Induced Pluripotent Stem Cell Derived Cardiomyocyte Electro-Mechanical Modelling and Simulation

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) enable accessible human-based cardiology studies. However, an immature hiPSC-CM electrophysiological and contractile phenotype hinders data translation to adult cardiomyocytes. In silico hiPSC-CM investigations could aid in hiPSC-CM data translation but most hiPSC-CM models do not feature a contractile element which limits their application for such studies. To address this issue, we have developed an electromechanical hiPSC-CM computer model by coupling an electrophysiological hiPSC-CM model and a human contractile machinery model. The newly established model has been calibrated using experimental hiPSC-CM data. We demonstrate that the computed active tension, calcium transient and action potential biomarkers agree with the experimental ranges. The peak twitch tension generated at 1 Hz pacing was 0.44 kPa which is in range with experimentally observed values (0.21-6.5 kPa). Comparisons with the adult myocyte electromechanical model demonstrate the potential usability of the hiPSC-CM model in the future data translation. Altogether, we present a new electromechanical hiPSC-CM model for comprehensive in silico hiPSC-CM-based studies.