Short-term Electrical Stimulation Impacts Cardiac Cell Structure and Function

Abstract

Induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) are used to model cardiac development and disease. This requires a robust population of mature CMs and external stimuli to mimic the complex environment of the heart. In effort toward this maturation, previous groups have applied electrical stimulation (ES) to CMs with varying results depending on the stimulation duration, frequency, and pattern. As such, there is uncertainty surrounding the timeline on which stimulated iPSC-CMs begin to show early signs of maturation in comparison to their non-stimulated counterparts, leaving room for additional research into when hallmarks of maturity-such as hypertrophy and changes to sarcomere structure-develop in CMs. Here, we introduce a low-cost custom bioreactor capable of delivering tunable electrical stimulation to standard 2D cell monolayers. We show that, after exposure to short-term ES, stimulated CMs express early signs of maturation compared to the non-stimulated control. The changes to contractility and protein expression indicate that the cells undergo hypertrophy in response to short-term ES, but they do not develop transverse-tubules, which is a key component of a fully mature CM structure. Therefore, while early signs of maturation are present after a short stimulation regimen, additional cellular structures must develop to reach complete maturation. We have shown that our custom electrical stimulator can be easily integrated with standard in vitro cell culture platforms to obtain measurable changes to cells, exhibiting its potential for promoting crucial CM maturation for cardiac tissue engineering applications.