Biphasic Electrical Pulse by a Micropillar Electrode Array Enhances Maturation and Drug Response of Reprogrammed Cardiac Spheroids

Direct reprogramming is an efficient strategy to produce cardiac lineage cells necessary for cardiac tissue engineering and drug testing for cardiac toxicity. However, functional maturation of reprogrammed cardiomyocytes, which is of great importance for their regenerative potential and drug response, still remains challenging. In this study, we propose a novel electrode platform to promote direct cardiac reprogramming and improve the functionality of reprogrammed cardiac cells. Nonviral cardiac reprogramming was improved via a three-dimensional spheroid culture of chemically induced cardiomyocytes exposed to a small-molecule cocktail. A micropillar electrode array providing biphasic electrical pulses mimicking the heartbeat further enhanced maturation and electrophysiological properties of reprogrammed cardiac spheroids, leading to proper responses and increased sensitivity to drugs. On the basis of our results, we conclude that our device may have a wider application in the generation of functional cardiac cells for regenerative medicine and screening of novel drugs.