Title:Maturation of Nephrons by Implanting hPSC-derived Kidney Progenitors
Under Kidney Capsules of Unilaterally Nephrectomized Mice
Volume: 18
Issue: 4
Author(s): Xin Yu, Shan Jiang, Kailin Li, Xianzhen Yang, Denglu Zhang, Xiaohang Du, Kong Feng and Shengtian Zhao*
Affiliation:
- Department of Urology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
- Engineering Laboratory of Urinary Organ and Functional Reconstruction of Shandong Province, Jinan, China
- Binzhou Medical University, Binzhou, China
Keywords:
Kidney, organoids, induced pluripotent stem cells, implantation, stromal expansion, polarization.
Abstract:
Background: Human pluripotent stem cell (hPSC)-derived kidney organoids may contribute to
disease modeling and the generation of kidney replacement tissues. However, the 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 short-term (2 weeks) implantation of hPSC-derived organoids below the kidney capsules of unilaterally
nephrectomized and immunodeficient mice resulted in the enlargement of organoids and production
of vascular cells, although signs of maturation were lacking.
Methods: Organoids were induced for 15 days in vitro and then grafted below kidney capsules of the
same unilaterally nephrectomized immunodeficient mouse model to examine whether medium-term (4
weeks) implantation could improve organoid maturation and vascularization, as evaluated by immunofluorescence
and transmission electron microscopy.
Results: We demonstrated that after 2–4 weeks of implantation, renal organoids formed host-derived
vascularization and matured without any exogenous vascular endothelial growth factor. Glomerular filtration
barrier maturation was evidenced by glomerular basement membrane deposition, perforated glomerular
endothelial cell development, and apical, basal podocyte polarization. A polarized monolayer epithelium
and extensive brush border were also observed for tubular epithelial cells.
Conclusions: Our results indicate that the in vivo microenvironment is important for the maturation of
human kidney organoids. Stromal expansion and a reduction of nephron structures were observed following
longer-term (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.
