Vascularizing organogenesis: Lessons from developmental biology and implications for regenerative medicine.

Organogenesis requires tightly coordinated and patterned growth of numerous cell types to form a fully mature and vascularized organ. Endothelial cells (ECs) that line blood vessels develop alongside the growing organ, but only recently has their role in directing epithelial and stromal growth been appreciated. Endothelial, epithelial, and stromal cells in embryonic organs actively communicate with one another throughout development to ensure that the organ forms appropriately. What signals tell blood vessel progenitors where to go? How are tissues influenced by the vasculature that pervades it? In this chapter, we review the ways in which crosstalk between ECs and epithelial or stromal cells during development leads to a fully patterned pancreas, lung, or kidney. ECs in all of these organs are necessary for proper epithelial and stromal growth, but how they direct this process is organ- and time-specific, highlighting the concept of dynamic EC heterogeneity. We end with a discussion on how understanding cell-cell crosstalk during development can be applied therapeutically through the generation of transplantable miniature organ-like tissues called "organoids." We will discuss the current state of organoid technology and highlight the major challenges in forming a properly patterned vascular network that will be critical in transforming them into a viable therapeutic option.