Modelling the electrophysiological interactions between human pluripotent cell-derived cardiomyocite grafts and host ventricular tissue
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are a promising therapy for regenerating myocardium after infarction, but their use is limited by graft-related arrhythmias that frequently occur shortly after transplantation. Experimental studies indicate that these arrhythmias can originate within the graft, which may act as an ectopic pacemaker, yet the mechanisms governing successful excitation of host tissue remain poorly understood. In particular, the role of electrical coupling at the graft-host interface is important, but difficult to measure directly or control. Computer modelling can help here. Here, we present a computational framework that enables systematic investigation of graft-host electrical interactions using a physiologically interpretable parameterisation. We model the graft-host interface as an internal boundary with a defined specific conductance, allowing direct control over coupling strength in units that correspond to measurable tissue properties. We formulate the governing equations and implement the computations using both finite-difference and finite-element discretisations in established cardiac modelling platforms. Using representative anatomical and physiological configurations, we demonstrate how variations in interface conductance influence the ability of spontaneous graft activity to initiate propagating excitation in host tissue. This framework provides a reproducible, mechanistically transparent tool for studying graft-related arrhythmogenesis and lays a foundation for evaluating strategies to mitigate arrhythmic risk in cardiac cell therapy.