Electrical conditioning of human stem cell-derived cardiomyocytes in three-dimensional culture promotes maturation and causes cells to adapt their autonomous beating rate to the stimulation frequency.
Does electrical stimulation promote maturation and regulate the intrinsic beating properties of human stem cell-derived cardiomyocytes?
Electrical conditioning of human stem cell-derived cardiomyocytes promotes structural and electrophysiological maturation, allowing them to adapt their autonomous beating rate, which may reduce arrhythmogenicity in future cell-based cardiac regeneration therapies.
The therapeutic success of human stem cell-derived cardiomyocytes critically depends on their ability to respond to and integrate with the surrounding electromechanical environment. Currently, the immaturity of human cardiomyocytes derived from stem cells limits their utility for regenerative medicine and biological research. We hypothesize that biomimetic electrical signals regulate the intrinsic beating properties of cardiomyocytes. Here we show that electrical conditioning of human stem cell-derived cardiomyocytes in three-dimensional culture promotes cardiomyocyte maturation, alters their automaticity and enhances connexin expression. Cardiomyocytes adapt their autonomous beating rate to the frequency at which they were stimulated, an effect mediated by the emergence of a rapidly depolarizing cell population, and the expression of hERG. This rate-adaptive behaviour is long lasting and transferable to the surrounding cardiomyocytes. Thus, electrical conditioning may be used to promote cardiomyocyte maturation and establish their automaticity, with implications for cell-based reduction of arrhythmia during heart regeneration.
Eng et al. (Tue,) conducted a other in Stem cell-derived cardiomyocytes. Electrical stimulation vs. Unstimulated control was evaluated on Spontaneous beating rate adaptation. Electrical conditioning of human stem cell-derived cardiomyocytes in three-dimensional culture promotes maturation and causes cells to adapt their autonomous beating rate to the stimulation frequency.