Journal
STEM CELL REPORTS
Volume 10, Issue 3, Pages 751-765Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2018.01.041
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Funding
- European Community's Seventh Framework Program (FP7) (Stem cell-based therapy for kidney repair, STELLAR, grant) [305436]
- European Community's Seventh Framework Program RECellularizing ORgan Donors for KIDney bioengineering (RECORD KID, Dutch Kidney Foundation) [15RN02]
- NIH [DK107344]
- National Health and Medical Research Council (NHMRC) [GNT1100970]
- Wiyadharma fellowship (Bontius Stichting, LUMC)
- Veni-grant from the Netherlands Organisation for Scientific Research (NWO) [016.176.081]
- Gisela Thier grant (LUMC)
- Leids Universiteits Fonds (LUF) [CWB 7204]
- Victorian Government's Operational Infrastructure Support Program
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [UH2DK107344, UH3DK107344] Funding Source: NIH RePORTER
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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.
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