Development of low-cost electrical stimulation device to promote hiPSC-CM differentiation and functionality

Human 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 human induced pluripotent stem cells during cardiac differentiation. Notably, our open-source device enables the generation of dynamic electrical stimulation regimens that may vary in frequency and pulse duration over time. Our results show that cardiac differentiation under dynamic electrical stimulation improves cardiac differentiation efficiency, beating synchronicity, and intracellular calcium handling and flow but impedes contraction compared to static electrical stimulation and no stimulation controls. We also show that pulse duration is an important stimulation parameter to optimize for hiPSC-CM differentiation and functionality. Across nearly all measured metrics, hiPSC-CMs subjected to dynamic pulse duration stimulation during differentiation outperformed those generated under dynamic frequency stimulation. We anticipate that more complex dynamic electrical stimulation regimens may be generated to further optimize hiPSC-CM functionality and maturity.