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Nat Mater. 2019 Apr;18(4):397-405. doi: 10.1038/s41563-019-0287-6. Epub 2019 Feb 18.

Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells.

Author information

1
Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Technology (BIST), Barcelona, Spain.
2
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Technology (BIST), Barcelona, Spain.
3
University of Barcelona, Barcelona, Spain.
4
Instituto de Biología Molecular de Barcelona (IBMB-CSIC), Parc Científic de Barcelona, Barcelona, Spain.
5
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain.
6
Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
7
Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain.
8
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
9
Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain.
10
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
11
Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Technology (BIST), Barcelona, Spain. nmontserrat@ibecbarcelona.eu.
12
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain. nmontserrat@ibecbarcelona.eu.
13
Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. nmontserrat@ibecbarcelona.eu.

Abstract

The generation of organoids is one of the biggest scientific advances in regenerative medicine. Here, by lengthening the time that human pluripotent stem cells (hPSCs) were exposed to a three-dimensional microenvironment, and by applying defined renal inductive signals, we generated kidney organoids that transcriptomically matched second-trimester human fetal kidneys. We validated these results using ex vivo and in vitro assays that model renal development. Furthermore, we developed a transplantation method that utilizes the chick chorioallantoic membrane. This approach created a soft in vivo microenvironment that promoted the growth and differentiation of implanted kidney organoids, as well as providing a vascular component. The stiffness of the in ovo chorioallantoic membrane microenvironment was recapitulated in vitro by fabricating compliant hydrogels. These biomaterials promoted the efficient generation of renal vesicles and nephron structures, demonstrating that a soft environment accelerates the differentiation of hPSC-derived kidney organoids.

PMID:
30778227
DOI:
10.1038/s41563-019-0287-6
[Indexed for MEDLINE]

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