Journal article
Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo
CW van den Berg, L Ritsma, MC Avramut, LE Wiersma, BM van den Berg, DG Leuning, E Lievers, M Koning, JM Vanslambrouck, AJ Koster, SE Howden, M Takasato, MH Little, TJ Rabelink
Stem Cell Reports | CELL PRESS | Published : 2018
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-exist..
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Awarded by Leids Universitair Medisch Centrum
Funding Acknowledgements
We thank Christian Freund (hiPSC core facility, LUMC, Leiden, the Netherlands) for providing two hiPSC lines (LUMC0072iCTRL01 and LUMC0099iCTRL04), Christine Mummery (LUMC, Leiden, the Netherlands) for providing hES3 ENVY, and Andrew Elefanty and Edouard Stanley (MCRI, Melbourne, Australia) for providing reporter hESC-SOX17-mCherry. We acknowledge the support of Maaike Hanegraaf, Angela Koudijs, Dorien Ward-van Oostwaard, Manon Zuurmond (LUMC, Leiden, the Netherlands), Caro Overmars-Bos and Joost Hoenderop (Radboud UMC, Nijmegen, the Netherlands), and Pei Er, Joanne Soo and Irene Ghobrial (MCRI, Melbourne, Australia). M.H.L. is a Senior Principal Research Fellow of the National Health and Medical Research Council of Australia (GNT1042093). Funding is from the European Community's Seventh Framework Program (FP7/2007-2013) (Stem cell-based therapy for kidney repair, STELLAR, grant agreement number 305436) and RECellularizing ORgan Donors for KIDney bioengineering (RECORD KID, Dutch Kidney Foundation, 15RN02), the NIH (DK107344), and the National Health and Medical Research Council (NHMRC, GNT1100970). C.W.v.d.B. is supported by the Wiyadharma fellowship (Bontius Stichting, LUMC). L.R. is supported by a Veni-grant from the Netherlands Organisation for Scientific Research (NWO, 016.176.081), the Gisela Thier grant (LUMC), and a subsidy from the Leids Universiteits Fonds (LUF, CWB 7204). MCRI is supported by the Victorian Government's Operational Infrastructure Support Program.