Human pluripotent stem cell -derived kidney organoids may contribute to
disease modeling and generation of kidney replacement tissues. However,
realization of such applications requires the induction of hPSCs into
functional mature organoids. One of the key questions for this process
is whether a specific vascular system exists for nephrogenesis. Our
previous study showed that implantation of hPSC-derived organoids below
the kidney capsules of unilaterally nephrectomized mice for 2 weeks
resulted in the enlargement of organoids and production of vascular
cells, although signs of maturation were lacking. In this study,
organoids are induced in vitro during 15 days and then sub-capsularly
grafted into kidneys, we used the same mice model to examine whether a 4
weeks implantation could improve organoid maturation and
vascularization, as evaluated by immunofluorescence and transmission
electron microscopy. We demonstrate that after 2–4 weeks implantation,
implanted renal organoids can form host-derived vascularization and
mature in the absence of any exogenous vascular endothelial growth
factor. Glomerular filtration barrier maturation was evidenced by
glomerular basement membrane deposition, perforated glomerular
endothelial cell development, as well as apical to basal podocyte
polarization. A polarized monolayer epithelium and extensive brush
border were also observed for tubular epithelial cells. Our results
indicate that the in vivo microenvironment is important for the
maturation of human kidney organoids. However, stromal expansion and a
reduction of nephron structures were observed following 12 weeks
implantation, suggesting effects on off-target cells during the
induction process. Accordingly, induction efficiency and transplantation
models should be improved in the future