Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo
Summary: 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...
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Elsevier
2018-03-01
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Series: | Stem Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671118300675 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cathelijne W. van den Berg Laila Ritsma M. Cristina Avramut Loes E. Wiersma Bernard M. van den Berg Daniëlle G. Leuning Ellen Lievers Marije Koning Jessica M. Vanslambrouck Abraham J. Koster Sara E. Howden Minoru Takasato Melissa H. Little Ton J. Rabelink |
spellingShingle |
Cathelijne W. van den Berg Laila Ritsma M. Cristina Avramut Loes E. Wiersma Bernard M. van den Berg Daniëlle G. Leuning Ellen Lievers Marije Koning Jessica M. Vanslambrouck Abraham J. Koster Sara E. Howden Minoru Takasato Melissa H. Little Ton J. Rabelink Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo Stem Cell Reports |
author_facet |
Cathelijne W. van den Berg Laila Ritsma M. Cristina Avramut Loes E. Wiersma Bernard M. van den Berg Daniëlle G. Leuning Ellen Lievers Marije Koning Jessica M. Vanslambrouck Abraham J. Koster Sara E. Howden Minoru Takasato Melissa H. Little Ton J. Rabelink |
author_sort |
Cathelijne W. van den Berg |
title |
Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo |
title_short |
Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo |
title_full |
Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo |
title_fullStr |
Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo |
title_full_unstemmed |
Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo |
title_sort |
renal subcapsular transplantation of psc-derived kidney organoids induces neo-vasculogenesis and significant glomerular and tubular maturation in vivo |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2018-03-01 |
description |
Summary: 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. : In this article, Van den Berg and colleagues show that PSC-derived kidney organoids contain nephron structures but remain disorganized and immature after prolonged culture. Upon transplantation, the organoids develop host-derived vascularization, functional glomerular perfusion, and connection to pre-existing vascular networks. The authors conclude that patent vasculature is required for ongoing morphogenesis and maturation of these kidney organoids. Keywords: human pluripotent stem cells, directed differentiation, kidney organoids, transplantation, intravital microscopy, vascularization, maturation |
url |
http://www.sciencedirect.com/science/article/pii/S2213671118300675 |
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doaj-a295322f3fb74a0cb7a83b492d7bebd92020-11-24T23:06:24ZengElsevierStem Cell Reports2213-67112018-03-01103751765Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In VivoCathelijne W. van den Berg0Laila Ritsma1M. Cristina Avramut2Loes E. Wiersma3Bernard M. van den Berg4Daniëlle G. Leuning5Ellen Lievers6Marije Koning7Jessica M. Vanslambrouck8Abraham J. Koster9Sara E. Howden10Minoru Takasato11Melissa H. Little12Ton J. Rabelink13Department 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; Corresponding authorDepartment of Cell and Chemical Biology, Cancer Genomics Centre Netherlands, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the NetherlandsDepartment 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 NetherlandsDepartment 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 NetherlandsDepartment 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 NetherlandsDepartment 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 NetherlandsDepartment 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 NetherlandsMurdoch Children’s Research Institute, Flemington Road, Parkville, VIC 3052, AustraliaDepartment of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the NetherlandsMurdoch Children’s Research Institute, Flemington Road, Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC 3010, AustraliaMurdoch Children’s Research Institute, Flemington Road, Parkville, VIC 3052, Australia; RIKEN Center for Developmental Biology, Chuou-ku, Kobe 650-0045, JapanMurdoch Children’s Research Institute, Flemington Road, Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC 3010, AustraliaDepartment 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 NetherlandsSummary: 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. : In this article, Van den Berg and colleagues show that PSC-derived kidney organoids contain nephron structures but remain disorganized and immature after prolonged culture. Upon transplantation, the organoids develop host-derived vascularization, functional glomerular perfusion, and connection to pre-existing vascular networks. The authors conclude that patent vasculature is required for ongoing morphogenesis and maturation of these kidney organoids. Keywords: human pluripotent stem cells, directed differentiation, kidney organoids, transplantation, intravital microscopy, vascularization, maturationhttp://www.sciencedirect.com/science/article/pii/S2213671118300675 |