Dynamic Electrical Stimulation Promotes hiPSC-CM Differentiation and Functionality

Abstract

AbstractHuman induced pluripotent stem cell differentiated cardiomyocytes (hiPSC-CMs) hold great potential to resolve cardiovascular disease but are stymied by their functional immaturity. The complex electric potentials measured during cardiogenesis point to the potential of exogenous electrical stimulation in improving cardiac differentiation and functionality. Herein, we create, validate, and implement a low-cost electrical stimulation device to stimulate hiPSCs during cardiac differentiation. Notably, our open-source device enables the generation of complex electrical stimulation regimes that may vary in frequency and pulse duration over time. Our results demonstrate that dynamic stimulation during differentiation improves cardiac differentiation efficiency, calcium handling, and flow velocity, and promotes significant transcriptomic pathway enrichment compared to static stimulation or no stimulation controls. Moreover, dynamic stimulation enhances electrochemical coupling and promotes the expression of cardiogenic pathways, potentially via sarcomere development. We anticipate that more complex dynamic electrical stimulation regimens may be generated to further optimize hiPSC-CM functionality and maturity.