Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo
Authorvan den Berg, CW; Ritsma, L; Avramut, MC; Wiersma, LE; van den Berg, BM; Leuning, DG; Lievers, E; Koning, M; Vanslambrouck, JM; Koster, AJ; ...
Source TitleStem Cell Reports
Document TypeJournal Article
Citationsvan den Berg, C. W., Ritsma, L., Avramut, M. C., Wiersma, L. E., van den Berg, B. M., Leuning, D. G., Lievers, E., Koning, M., Vanslambrouck, J. M., Koster, A. J., Howden, S. E., Takasato, M., Little, M. H. & Rabelink, T. J. (2018). Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo. STEM CELL REPORTS, 10 (3), pp.751-765. https://doi.org/10.1016/j.stemcr.2018.01.041.
Access StatusOpen Access
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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