From Ionic Dynamics to Tissue Electrophysiology in Stem Derived Cardiomyocytes

Cardiac electrophysiology in regenerative medicine is modeled across scales, from ionic currents in single cells to electrical propagation in heterogeneous cardiac tissues. The focus is on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), widely used for drug testing and disease modeling despite their immature and highly variable electrophysiological properties. Starting from ventricular-like and atrial-like ionic models with detailed descriptions of membrane currents and calcium handling, these formulations enable the study of phenotype-specific and pathological mechanisms. These models link ionic dynamics to tissue-scale behavior. However, variability—particularly in senescent hiPSC-CMs—turns parameter identification from experimental recordings into an inverse problem. Neural network emulators are used to infer ionic conductances directly from signals, enabling efficient exploration of heterogeneous cellular populations. Cell populations are then embedded into 2D heterogeneous tissues, where electrical propagation and extracellular signals are simulated using continuum formulations inspired by the bidomain framework and adapted to Multi-Electrode Array systems. This connects cellular variability to measurable extracellular activity and allows tracking of how ionic perturbations propagate at tissue level. Within this framework, pharmacological effects are simulated via ionic modulation, while diseases such as Brugada Syndrome are reproduced from cell to tissue scale, linking ionic dysfunction to emergent electrophysiological patterns.

Seminario nell'ambito del corso "Cardiac Modelling"