Apr 26, 2022
Two chapters in the latest volume of the Current Topics in Developmental Biology series were authored and co-edited by members of the RBK project, Visualizing Vascularization and Cell Interactions in Implanted Organoids.
Ondine Cleaver and junior investigator Annie Ryan authored Chapter Seven - Plumbing our organs: Lessons from vascular development to instruct lab generated tissues.
Leif Oxburgh is co-editor of the book and wrote Chapter Nine - Growth control of the kidney.
Ryan, Anne R.; Cleaver, Ondine. Current Topics in Developmental Biology. 148:165–194. 2022.
Abstract: 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.
Oxburgh, Leif. Current Topics in Developmental Biology. 148:237–263. 2022.
Abstract: The functional mass of kidney tissue in an adult is an important determinant of human health. Kidney formation during development is an essential determinant of the final nephron endowment of the adult organ, and no evidence has been reported that mice or humans are able to generate new nephrons after the developmental period. Mechanisms controlling organ growth after development are essential to establish the final adult organ size. The potential for organ growth is maintained in adult life and the size of one kidney may be significantly increased by loss of the contralateral kidney. The mouse has provided a model system for investigators to critically explore genetic, cell biological, and hormonal control of developmental and juvenile kidney growth. This article reviews three basic aspects of kidney size regulation: (1) Mechanisms that control nephron formation and how these are altered by the cessation of nephrogenesis at the end of the developmental period. (2) Applicability of the general model for growth hormone-insulin like growth factor control to kidney growth both pre- and postnatally. (3) Commonalities between mechanisms of juvenile kidney growth and the compensatory growth that is stimulated in adult life by reduction of kidney mass. Understanding the mechanisms that determine set-points for cell numbers and size in the kidney may inform ongoing efforts to generate kidney tissue from stem cells.