Reverse engineering the human heart with pluripotent stem cells

Recent advances in stem cell technologies, synthetic development and organoid biology are enabling us to create more accurate in vitro models of human organs. Here we will discuss methods to generate developmentally relevant human heart organoids by self-organization strategies using human pluripotent stem cells. Our procedure is fully defined, efficient, reproducible, and compatible with high-content approaches. These organoids develop sophisticated internal chambers with well-organized multi-lineage cardiac cell types, recapitulate heart field formation, atrioventricular specification, develop a complex vasculature, anterio-posterior heart patterning, and exhibit robust functional activity. We also show that our organoid platform can recreate complex metabolic disorders associated with congenital heart defects.