Kidney organoid vascularization: current advancements in the field

Abstract

Kidney organoids have the possibility to vastly advance renal medicine, both as an organ model and as a cell source for regenerative medicine. While significant improvements have been made in recreating organ specific lineages, one area that still demands improvement is vascularization. Specifically, glomerular vascularization, an indispensable factor for renal function, has seldom been achieved in vitro. In this review, we summarize current research on this field. We first outline the contemporary understanding of renal development, as well as its implications on kidney organoid vascularization. Two important aspects warrant particular attention; the origin of endothelial cells during vascularization, and the mechanisms of glomerular vascularization. We then present the diverse strategies that aim for kidney organoid vascularization, both in vivo and in vitro. While in vivo approaches have been better in achieving glomerular vascularization, a few reports have been successful in vascularizing glomeruli in vitro by utilizing conditions such as flow, and endothelial niche induction. Finally, we introduce fields of research that could potentially be integrated to further improve vascularization and maturation. These include methods such as focusing on endothelial cell phenotypes as was done in vascularization of other organoid types, introduction of non-parenchymal cell types, and general scale-up of production, culture, and analysis of kidney organoids.