Generation of human iPSCs derived heart organoids structurally and functionally similar to heart

Abstract

Currently, due to the increasing demand for 3D culture, various organoids that mimic organs are being actively studied. Despite active reports, information on heart organoids (HOs), which are the first functional organs, is still insufficient. Parameters for reproducing hearts are: chamber formation, organization with cardiac cells, vascularization, and simulation of electrophysiological signals. In particular, since the heart reflects complex factors, it is necessary to develop HOs that can be simulated in depth. In this study, we have created self-organized HOs using human iPSCs, and validated mimicry of cardiac structures such as chamber and epicardium/myocardium and atrium/ventricle-similar areas. Furthermore, mechanical/electrophysiological features were verified through multiple analyzes after inhibition of ion channels. More importantly, the HOs function, due to the cardiovascular characteristics of HOs, was maintained through vascularization after in vivo transplantation. In conclusion, this study has the advantage of being able to easily and closely recapitulate morphological/functional aspects of the heart.

Keywords: Cardiogenesis; Chamber formation; Electrophysiological analysis; Epicardium; Heart organoid; Human induced pluripotent stem cells; Mechanical analysis; Myocardium; Vascularization.