Cardio-Vessel Organoids (CVO) generated from pluripotent stem cell for modelling the cardiovascular system in vitro and revealing the cardiovascular toxicity of drugs.

Cardiovascular toxicity is a leading cause of drug attrition. Conventional animal models are constrained by cost, duration, and interspecies discrepancies. Organoids provide physiologically relevant alternatives for toxicity assessment. Here, we developed cardiovascular organoids (CVOs) by co-differentiating cardiomyocytes and vascular progenitor cells from human embryonic stem cells. CVOs demonstrated enhanced vascular and myocardial maturation relative to standalone cardiomyocyte or vascular organoids. In pharmacological assays, CVOs accurately recapitulated amiodarone bleomycin and cisplatin induced endothelial stress and captured dexamethasone and Vitamin C anti-inflammatory and antioxidant properties. CVOs generated results consistent with established toxicity profiles, exhibiting superior discriminatory capacity between positive and negative compounds. The prediction accuracy of the selected specific markers for all model compounds was about 90%. These findings confirm that CVOs reliably mirror in vitro cardiovascular toxicity profiles and represent a human-relevant platform for first-line screening of compounds.