Key result
In silico optimization of stem cell-derived cardiomyocytes cuts arrhythmia re-entry window by ~95%.
Why the study?
Regenerative cell therapy for myocardial infarction is limited clinically because delivered cells may beat spontaneously and cause ventricular arrhythmias.
Does optimizing ionic currents in hPSC-CMs reduce arrhythmic burden in in silico models of infarcted human ventricles?
Does optimizing ionic currents in hPSC-CMs reduce arrhythmic burden in in silico models of infarcted human ventricles?
Computational modeling demonstrates that concurrently targeting specific ionic currents in stem cell-derived cardiomyocytes can mitigate automaticity and re-entry arrhythmias post-myocardial infarction.
May reduce simulated arrhythmic risk after cell therapy; leaves open in vivo translation and clinical adoption.
Myocardial infarction remains a frequent cause of heart failure and mortality. Cell therapy has shown promise in regenerating the damaged tissue, but delivered cells may beat spontaneously and produce ventricular arrhythmias, hindering clinical application. Here, we conducted multiscale computer simulations of the electrical activity of the infarcted human ventricles including the cardiac conduction system to identify and mitigate pro-arrhythmic mechanisms following cell delivery. Firstly, our simulations show how arrhythmic risk increases from before to after cell injection and further during the first two weeks post-delivery. Secondly, we suggest that concurrently targeting the funny current, the inward rectifier potassium current, the sodium-potassium pump current, and the rapid delayed outward rectifier potassium current may reduce automaticity and re-entry while maximizing calcium transient amplitude and thus contractility. Our study demonstrates how modeling and simulation enables the design of anti-arrhythmic strategies to improve therapy safety while preserving efficacy.
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Riebel et al. (2026) studied Myocardial infarction (in silico models). In silico optimization of ionic targets (funny current block, upscaling sodium-potassium pump and potassium currents) vs. Unoptimized baseline stem cell-derived cardiomyocytes was evaluated on Vulnerable window for re-entry at day 14 post-delivery. In silico optimization of stem cell-derived cardiomyocytes by targeting specific ionic currents decreased the re-entry vulnerable window from 2,080 to 100 ms at day 14 post-delivery.
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