Vascular organoids in cardiovascular medicine: From stem cell biology to precision medicine

Abstract

Cardiovascular diseases remain the leading cause of death worldwide. However, conventional therapies incompletely address disease heterogeneity, and conventional in vitro models do not accurately recapitulate the complex vascular microenvironment. Embryonic stem cells, induced pluripotent stem cells, and adult stem cells, including adipose-derived mesenchymal stem cells and bone marrow mesenchymal stem cells, provide a robust cellular foundation for constructing functional vascular networks through multidirectional differentiation and paracrine signaling. Advanced technologies for generating vascularized organoids, including co-culture systems, bioprinting, and growth factor modulation, have markedly enhanced organoid survival, structural stability, and physiological fidelity. These organoids have enabled the formation of functional vascular networks in multiple organ systems, including the brain, kidney, and heart, while faithfully reproducing both disease-associated pathological features and normal physiological functions. As a result, they serve as versatile platforms for investigating mechanisms of vascular disease, performing high-throughput drug screening, evaluating drug efficacy and toxicity, and developing personalized therapeutic strategies. Furthermore, vascularized organoids facilitate mechanistic studies on angiogenesis, vascular remodeling, and cell–cell interactions within physiologically relevant three-dimensional contexts, offering insights that are difficult to obtain from conventional two-dimensional cultures or animal models. This review systematically summarizes the roles of various stem cells in angiogenesis, outlines strategies for constructing vascularized organoids, and highlights their emerging applications in modeling vascular-associated diseases and regenerative therapy, providing a comprehensive reference for advancing both basic research and clinical translation in vascular medicine.