Kidney organoids for disease modeling

Abstract

The kidney is formed during development by reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (MM), which promote the induction of nephron patterning and differentiation. Traditionally, UB and MM cells including nephron progenitor cells (NPCs) have been very difficult to isolate and maintain in culture due to their propensity to differentiate when outside their developmental niche. Remarkably, in recent years researchers have succeeded in prolonging the lifespan of mouse [1], rat [1], and human [2] NPCs in vitro, offering an avenue to expand the current knowledge of mammalian kidney development, and eventually for disease modelling and drug screening studies. Alternatively, renal progenitors have also been generated from human pluripotent stem cells (hPSCs) by mimicking early kidney developmental signals in vitro. Recently, different laboratories have been able to partially reproduce kidney organogenesis in a dish using hPSCs, successfully generating so-called kidney organoids [3,4,5,6]. Kidney organoids contain self-organized nephron-like structures composed of early podocyte cell clusters connected to tubular structures expressing markers of proximal tubules, loops of Henle and distal tubules [3,4,5,6]. In addition, kidney organoids display proximal tubular functionality in vitro, showing selective endocytosis of dextran cargoes [5,6], as well as responding to nephrotoxic agents [4,5,6].