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Stem Cell Reports. 2018 Mar 13;10(3):751-765. doi: 10.1016/j.stemcr.2018.01.041. Epub 2018 Mar 1.

Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo.

Author information

1
Department of Internal Medicine - Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. Electronic address: c.w.van_den_berg@lumc.nl.
2
Department of Cell and Chemical Biology, Cancer Genomics Centre Netherlands, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
3
Department of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
4
Department of Internal Medicine - Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
5
Murdoch Children's Research Institute, Flemington Road, Parkville, VIC 3052, Australia.
6
Murdoch Children's Research Institute, Flemington Road, Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC 3010, Australia.
7
Murdoch Children's Research Institute, Flemington Road, Parkville, VIC 3052, Australia; RIKEN Center for Developmental Biology, Chuou-ku, Kobe 650-0045, Japan.

Abstract

Human pluripotent stem cell (hPSC)-derived kidney organoids may facilitate disease modeling and the generation of tissue for renal replacement. Long-term application, however, will require transferability between hPSC lines and significant improvements in organ maturation. A key question is whether time or a patent vasculature is required for ongoing morphogenesis. Here, we show that hPSC-derived kidney organoids, derived in fully defined medium conditions and in the absence of any exogenous vascular endothelial growth factor, develop host-derived vascularization. In vivo imaging of organoids under the kidney capsule confirms functional glomerular perfusion as well as connection to pre-existing vascular networks in the organoids. Wide-field electron microscopy demonstrates that transplantation results in formation of a glomerular basement membrane, fenestrated endothelial cells, and podocyte foot processes. Furthermore, compared with non-transplanted organoids, polarization and segmental specialization of tubular epithelium are observed. These data demonstrate that functional vascularization is required for progressive morphogenesis of human kidney organoids.

KEYWORDS:

directed differentiation; human pluripotent stem cells; intravital microscopy; kidney organoids; maturation; transplantation; vascularization

PMID:
29503086
PMCID:
PMC5918682
DOI:
10.1016/j.stemcr.2018.01.041
[Indexed for MEDLINE]
Free PMC Article

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