Chapter 34 - From Development to Regeneration: Kidney Reconstitution In vitro and In vivo

Abstract

The kidney develops through interactions between two precursor tissues: the metanephric mesenchyme and the ureteric bud; the former contains nephron progenitors that give rise to glomeruli and renal tubules. We present a revised model of early stage kidney specification: The metanephric mesenchyme is derived from a T-positive population located at the posterior end of the embryo in the postgastrulation stage, whereas the ureteric bud is derived from Osr1-positive anterior intermediate mesoderm. This model enables the induction of metanephric nephron progenitors from both mouse and human pluripotent stem cells. Upon Wnt stimulation, the induced progenitors reconstitute three-dimensional nephron structures, including both glomeruli with podocytes and nephric tubules with a clear lumina. The generation of three-dimensional nephron structures from human induced pluripotent stem cells will be useful for future application in regenerative therapy and modeling of congenital kidney diseases in vitro. This review summarizes the important findings in developmental biology that contribute to this newly established protocol and discusses the possibility of de novo organogenesis of a functional kidney both in vitro and in vivo.