In vitro generation of human embryonic stem cell-derived heart organoids possessing physiological ion currents

Abstract

Recently, methods for in vitro organogenesis have been broadly developed due to their strong potential for human applications in medicine. In the present study, we optimized the culturing method of human heart organoids (hHOs) from embryonic stem cells (ESCs) in the presence of the highly concentrated laminin-entactin and fibroblast growth factor 4. The resulting hHOs showed distinctive cardiac morphology with atrium- and ventricle-like chambers composed of cardiac cells as well as expressed the integral proteins of gap junctions and ion channels. In fact, isolated cardiomyocytes from these hHOs exhibited Na and Ca currents by patch clamp analysis. These results indicated that the present method will provide a powerful tool for cardiac safety assessment of newly developed drugs as an in vitro human ESC-derived test system. One-Sentence SummaryFGF4 and ECM contribute to the generation of human HOs with heart compartments and electrophysiological properties.