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Journal Articles NPJ Regenerative medicine Year : 2022

Vasculogenesis in kidney organoids upon transplantation

Marije Koning
Sébastien Dumas
M. Cristina Avramut
  • Function : Author
Roman Koning
Elda Meta
  • Function : Author
Ellen Lievers
  • Function : Author
Loes Wiersma
  • Function : Author
Mila Borri
Lin Xie
  • Function : Author
Ping Liu
  • Function : Author
Yonglun Luo
Jaap Mulder
H. Siebe Spijker
Bernard van den Berg
Cathelijne van den Berg
Ton Rabelink
  • Function : Author

Abstract

Abstract Human induced pluripotent stem cell-derived kidney organoids have potential for disease modeling and to be developed into clinically transplantable auxiliary tissue. However, they lack a functional vasculature, and the sparse endogenous endothelial cells (ECs) are lost upon prolonged culture in vitro, limiting maturation and applicability. Here, we use intracoelomic transplantation in chicken embryos followed by single-cell RNA sequencing and advanced imaging platforms to induce and study vasculogenesis in kidney organoids. We show expansion of human organoid-derived ECs that reorganize into perfused capillaries and form a chimeric vascular network with host-derived blood vessels. Ligand-receptor analysis infers extensive potential interactions of human ECs with perivascular cells upon transplantation, enabling vessel wall stabilization. Perfused glomeruli display maturation and morphogenesis to capillary loop stage. Our findings demonstrate the beneficial effect of vascularization on not only epithelial cell types, but also the mesenchymal compartment, inducing the expansion of ´on target´ perivascular stromal cells, which in turn are required for further maturation and stabilization of the neo-vasculature. The here described vasculogenic capacity of kidney organoids will have to be deployed to achieve meaningful glomerular maturation and kidney morphogenesis in vitro.

Dates and versions

hal-03996400 , version 1 (19-02-2023)

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Marije Koning, Sébastien Dumas, M. Cristina Avramut, Roman Koning, Elda Meta, et al.. Vasculogenesis in kidney organoids upon transplantation. NPJ Regenerative medicine, 2022, 7 (1), pp.40. ⟨10.1038/s41536-022-00237-4⟩. ⟨hal-03996400⟩
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