Vascularization of organoid microenvironments: Perfusable networks for organoid growth and maturation

Generation of functional vasculature within organoids is considered important for their development and maturation. However, direct differentiation of endothelial cells (ECs) in organoids remains challenging so that creating fully perfusable vasculature often still requires transplantation into host animals. This review discusses recent strategies for generating pre-vascularized human pluripotent stem cell (hPSC)-derived organoids, that include co-differentiation of ECs using growth factors or (an inducible transcription factor) ETV2, controlled assembly of tissue organoids with hPSC-derived ECs or Blood Vessel Organoids (BVOs), and 3D bioprinting. Additionally, the potential and key challenges of organ-on-chip technology for creating perfusable and functional vascular networks in organoids are explored, highlighting their implications for advancing research and improving experimental models of human tissue and disease.