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 an uncertainty surrounding the timeline on which stimulated iPSC-CMs begin to show early signs of maturation in comparison with their nonstimulated counterparts. Here, we introduce a low-cost custom bioreactor capable of delivering tunable ES to standard 2D cell monolayers. We show that, after exposure to short-term ES, stimulated CMs express early signs of maturation compared to nonstimulated controls. Changes to contractility and protein expression indicate cellular rearrangement within cell monolayers and induction of partial maturation in response to ES. While early signs of maturation are present after 3-4 days of ES, additional cellular structures must develop to reach complete maturation. We also show that this bioreactor can electrically stimulate cardiac fibroblasts (cFBs) and may induce alignment of cFB. We have shown that our custom ES bioreactor can be easily integrated into standard in vitro cell culture platforms to induce measurable changes in both CMs and cFB, exhibiting its potential for promoting crucial CM maturation and cell alignment for cardiac tissue engineering applications.