Plumbing our organs: Lessons from vascular development to instruct lab generated tissues.

The formation, growth and maintenance of our organs, such as our kidneys or pancreas, requires their coordinated growth alongside the intricate vasculature that pervades them. Blood vessels course through nearly every tissue in our bodies, facilitating the essential exchange of gases, nutrition and wastes, as well as the rapid circulation of hormones and other signaling molecules. Endothelial cells (ECs) that line all of our blood vessels are therefore the gatekeepers for communication between the circulation and organ-specific cell types. We and many others have sought to understand: (1) how endothelial cell progenitors initially assemble to form blood vessels in the embryo, and (2) how the embryonic vascular tree expands to perfuse growing organs. Here, we review what we have learned from embryonic blood vessels and how this knowledge instructs our approaches to vascularize laboratory generated tissues, such as organoids. We will assess our general understanding of blood vessel formation, and discuss recent studies of the growing kidney vasculature. Furthermore, we will assess the challenges and limitations faced by organoid technologies, including the difficulties in achieving the patterned vascular network that is essential to organ function. Lastly, we will then review recent studies of kidney organoid blood vessels and propose approaches that improve vascularization. Understanding the ontogeny of organ-specific vasculatures will help propel regenerative therapeutic approaches.

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