At SCERG-iBB it was recently established an epicardium/myocardium organoid model (hEMOs) from human pluripotent stem cells through an innovative co-culture strategy between myocardium organoids, mostly composed of cardiomyocytes, and pro-epicardium organoids. This innovative model presents for the first time 1) a self-organized continuous epicardial layer completely surrounding the myocardium-like region, and 2) the presence of fibroblast and vascular cells derived from the epicardial structure. However, the establishment of heart organoids recreating myocardium innervation was still not achieved. The major objective of the Nervous Heart project is the development of a vascularized and innervated ventricular heart organoid model by recreating the processes that occur in vivo during the respective time frame of embryonic heart development by leveraging on our recently established EMOs. As our final goal we expect to 1) obtain a model that will give unprecedented access to the mechanisms involved in the establishment of human ventricle myocardium innervation, and 2) explore the applicability of the developed innervated ventricle heart model to study the cellular mechanisms underlying the nervous system regulation of heart function in physiologic and pathologic conditions. We will specifically focus on arrhythmic events since these are typically associated with highly prevalent diseases such as myocardial infarction.