Returning to kidney development to deliver synthetic kidneys

Abstract

There is no doubt that the development of transplantable synthetic kidneys could improve the outcome for the many millions of people worldwide suffering from chronic kidney disease. Substantial progress has been made in the last 6 years in the generation of kidney tissue from stem cells. However, the limited scale, incomplete cellular complexity and functional immaturity of such structures suggests we are some way from this goal. While developmental biology has successfully guided advances to date, these human kidney models are limited in their capacity for ongoing nephrogenesis and lack corticomedullary definition, a unified vasculature and a coordinated exit path for urinary filtrate. This review will reassess our developmental understanding of how the mammalian embryo manages to create kidneys, how this has informed our progress to date and how both engineering and developmental biology can continue to guide us towards a synthetic kidney.

Keywords: Directed differentiation; Kidney development; Organogenesis; Organoid; Pluripotent stem cell; Synthetic embryology.