Generation of human chambered cardiac organoids from pluripotent stem cells for improved modelling of cardiovascular diseases

hPSC-CM has been used to model cardiac-related disease phenotypes. However, hPSC-CMs constrains their potential in cell-based therapy, disease modeling and drug discovery. Engineered heart tissues (EHT) or scaffold generated structures are unable to recapitulate the cardiovascular systems sufficiently to improve clinical reliance. Hence in this study, we demonstrate the Overall design: Utilizing human embryonic stem cells, chambered cardiac organoids (CCOs) were generated. Single cell RNA sequencing was performed on day8, day14 and day 21 of the CCOs differentiation. RNA-sequencing confirmed the presence of various cell types, such as smooth muscle cells, endothelial cells, cardiomyocytes and cardiac fibroblasts. We also demonstrated the utility of CCOs in modelling cardiac related disease, cardiac hypertrophy (CH). CH was modelled using endothelin-1, a known inducer of CH and its associated phenotypes. CCOs demonstrated capability of modelling functional dysregulation such as ejection fraction, thickening of cardiac chamber and arrythmic tendencies.