Abstract:
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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]. |