02054nas a2200217   4500000000100000008004100001260001500042653001800057653002400075653002100099653002500120653001400145653002200159100002100181700002300202245005500225856007000280300001200350490000800362520146600370       2023                            d  c2023-02-1710aBlood Vessels10aBlood-Brain Barrier10aendothelial cell10aextracellular matrix10aorganoids10avascular diseases1 aKirill Salewskij1 aJosef M. Penninger00aBlood Vessel Organoids for Development and Disease  uhttps://www.ahajournals.org/doi/abs/10.1161/CIRCRESAHA.122.321768  a498-5100 v1323 aDespite enormous advances, cardiovascular disorders are still a major threat to global health and are responsible for one-third of deaths worldwide. Research for new therapeutics and the investigation of their effects on vascular parameters is often limited by species-specific pathways and a lack of high-throughput methods. The complex 3-dimensional environment of blood vessels, intricate cellular crosstalks, and organ-specific architectures further complicate the quest for a faithful human in vitro model. The development of novel organoid models of various tissues such as brain, gut, and kidney signified a leap for the field of personalized medicine and disease research. By utilizing either embryonic- or patient-derived stem cells, different developmental and pathological mechanisms can be modeled and investigated in a controlled in vitro environment. We have recently developed self-organizing human capillary blood vessel organoids that recapitulate key processes of vasculogenesis, angiogenesis, and diabetic vasculopathy. Since then, this organoid system has been utilized as a model for other disease processes, refined, and adapted for organ specificity. In this review, we will discuss novel and alternative approaches to blood vessel engineering and explore the cellular identity of engineered blood vessels in comparison to in vivo vasculature. Future perspectives and the therapeutic potential of blood vessel organoids will be discussed.