Endothelial specialization and angiocrine factors are critical for vascularized organoid models.

A vast network of vessels and capillaries is required in most organs because effective diffusion is typically limited to less than 200 μm. Most tissue engineering efforts have focused on re-creating vascularized networks to overcome this size barrier, but critically, the vasculature performs many other roles in development, homeostasis, disease, immune responses, and cancer via "angiocrine" interactions. Vascularized organoids will provide a new capability to test the importance of angiocrine interactions, which can be challenging to disentangle from their impacts on perfusion or substrate provision in vivo. However, the usefulness of vascularized organoids will first require careful optimization of the organ-specific vascular phenotypes. Improved understanding of the organ-specific identities and functions of endothelial cells in physiological and diseased states will, in turn, enable accurate modeling and perturbation in vascularized organoids in vitro-with the potential to revolutionize the study of angiocrine function.