Formation of an electrical coupling between differentiating cardiomyocytes

Abstract

AbstractHuman induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) serve as an indispensable platform for the study of human cardiovascular disease is human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs). While the possibility of reproducing rare pathologies, patient-specific selection of drugs, and other issues concerning single cardiomyocytes have been well studied, little attention has been paid to the properties of the whole syncytium of CMs, in which both the functionality of individual cells and the distribution of electrophysiological connections between them are essential. The aim of this work is to directly study the ability of hiPSC-CMs to form a functional syncytium that can stably conduct an excitation wave. For that purpose, syncytium forming hiPSC-CMs were harvested and seeded (transferred) on a new substrate on different days of differentiation. The excitation conduction in a sample was characterized by the stability of the wavefront using optical mapping data. We found that the cells transferred before the 20th day of differentiation were able to organize a functional syncytium capable of further development and stable excitation conduction at high stimulation frequencies, while the cells transferred after 20 days did not form a homogeneous syncytium, and multiple instabilities of the propagating wavefront were observed with the possibility of reentry formation.