Flow-enhanced vascularization and maturation of kidney organoids in vitro.
Authors Homan KA, Gupta N, Kroll KT, Kolesky DB, Skylar-Scott M, Miyoshi T, Mau D,
Valerius MT, Ferrante T, Bonventre JV, Lewis JA, Morizane R
Submitted By Submitted Externally on 4/8/2019
Status Published
Journal Nature methods
Year 2019
Date Published 3/1/2019
Volume : Pages 16 : 255 - 262
PubMed Reference 30742039
Abstract Kidney organoids derived from human pluripotent stem cells have glomerular- and
tubular-like compartments that are largely avascular and immature in static
culture. Here we report an in vitro method for culturing kidney organoids under
flow on millifluidic chips, which expands their endogenous pool of endothelial
progenitor cells and generates vascular networks with perfusable lumens
surrounded by mural cells. We found that vascularized kidney organoids cultured
under flow had more mature podocyte and tubular compartments with enhanced
cellular polarity and adult gene expression compared with that in static
controls. Glomerular vascular development progressed through intermediate stages
akin to those involved in the embryonic mammalian kidney's formation of
capillary loops abutting foot processes. The association of vessels with these
compartments was reduced after disruption of the endogenous VEGF gradient. The
ability to induce substantial vascularization and morphological maturation of
kidney organoids in vitro under flow opens new avenues for studies of kidney
development, disease, and regeneration.