Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells

Anwar A. Palakkan; Julia Tarnick; Martin Waterfall; May Sallam; Fokion Glykofrydis; Mona Elhendawi; Jamie A. Davies

doi:10.1038/s41598-022-16768-1

Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells

Anwar A. Palakkan, Julia Tarnick, Martin Waterfall, May Sallam, Fokion Glykofrydis, Mona Elhendawi, Jamie A. Davies

Research output: Contribution to journal › Article › peer-review

Abstract

There is intense worldwide effort in generating kidney organoids from pluripotent stem cells, for research, for disease modelling and, perhaps, for making transplantable organs. Organoids generated from pluripotent stem cells (PSC) possess accurate micro-anatomy, but they lack higher-organization. This is a problem, especially for transplantation, as such organoids will not be able to perform their physiological functions. In this study, we develop a method for generating murine kidney organoids with improved higher-order structure, through stages using chimaeras of ex-fetu and PSC-derived cells to a system that works entirely from embryonic stem cells. These organoids have nephrons organised around a single ureteric bud tree and also make vessels, with the endothelial network approaching podocytes.

Original language	English
Article number	12573
Number of pages	16
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-16768-1
Publication status	Published - 22 Jul 2022

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10.1038/s41598-022-16768-1Licence: Creative Commons: Attribution (CC-BY)

DaviesEtalSR2022ProductionOfKidneyOrganoidsArrangeAdroundSingleUretericFinal published version, 7.41 MBLicence: Creative Commons: Attribution (CC-BY)

Advancing renal tissue engineering: equipping tissue-engineered kidneys with a ureter
Davies, J. (Principal Investigator)
MRC
1/02/19 → 30/04/22
Project: Research
Advancing construction of human induced pluripotent stem cell (iPSC)-derived kidneys from current crude organoids to making anatomically realistic mini-organs.
Davies, J. (Principal Investigator)
UK-based charities
27/02/17 → 31/12/19
Project: Research
SynthSys-Mammalian: Edinburgh Mammalian Synthetic Biology Research Centre
Danos, V. (Principal Investigator)
BBSRC
14/11/14 → 31/03/22
Project: Research

Cite this

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title = "Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells",

abstract = "There is intense worldwide effort in generating kidney organoids from pluripotent stem cells, for research, for disease modelling and, perhaps, for making transplantable organs. Organoids generated from pluripotent stem cells (PSC) possess accurate micro-anatomy, but they lack higher-organization. This is a problem, especially for transplantation, as such organoids will not be able to perform their physiological functions. In this study, we develop a method for generating murine kidney organoids with improved higher-order structure, through stages using chimaeras of ex-fetu and PSC-derived cells to a system that works entirely from embryonic stem cells. These organoids have nephrons organised around a single ureteric bud tree and also make vessels, with the endothelial network approaching podocytes.",

author = "Palakkan, {Anwar A.} and Julia Tarnick and Martin Waterfall and May Sallam and Fokion Glykofrydis and Mona Elhendawi and Davies, {Jamie A.}",

note = "Funding Information: The research leading to these results have received support from Kidney Research UK (grant RP_002_20160223), The Biotechnology and Biology Research Council (BBSRC) (grant BB/M018040/1) and the Medical Research Council (grant MR/R026483/1). Funding Information: We acknowledge Prof. Elaine Dzierzak (University of Edinburgh), Prof. John Mason (University of Edinburgh) and Prof. Ryuichi Nishinakamura (Kumamoto University) for providing mESC lines IB10, Hoxb7-Gfp and E14 respectively; Prof. Tung-Tien Sun (New York University) for providing Uroplakin antibody. We also acknowledge Confocal (IMPACT, Centre for Discovery Brain Sciences), Flow Cytometry (Ashworth Laboratories, Institute of Immunology & Infection Research) and RNA sequencing (Edinburgh Genomics) facilities of University of Edinburgh. Help from Dr. Frances Turner, Edinburgh Genomics in RNA sequence data analysis is also acknowledged. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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AU - Palakkan, Anwar A.

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AU - Waterfall, Martin

AU - Sallam, May

AU - Glykofrydis, Fokion

AU - Elhendawi, Mona

AU - Davies, Jamie A.

N1 - Funding Information: The research leading to these results have received support from Kidney Research UK (grant RP_002_20160223), The Biotechnology and Biology Research Council (BBSRC) (grant BB/M018040/1) and the Medical Research Council (grant MR/R026483/1). Funding Information: We acknowledge Prof. Elaine Dzierzak (University of Edinburgh), Prof. John Mason (University of Edinburgh) and Prof. Ryuichi Nishinakamura (Kumamoto University) for providing mESC lines IB10, Hoxb7-Gfp and E14 respectively; Prof. Tung-Tien Sun (New York University) for providing Uroplakin antibody. We also acknowledge Confocal (IMPACT, Centre for Discovery Brain Sciences), Flow Cytometry (Ashworth Laboratories, Institute of Immunology & Infection Research) and RNA sequencing (Edinburgh Genomics) facilities of University of Edinburgh. Help from Dr. Frances Turner, Edinburgh Genomics in RNA sequence data analysis is also acknowledged. Publisher Copyright: © 2022, The Author(s).

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N2 - There is intense worldwide effort in generating kidney organoids from pluripotent stem cells, for research, for disease modelling and, perhaps, for making transplantable organs. Organoids generated from pluripotent stem cells (PSC) possess accurate micro-anatomy, but they lack higher-organization. This is a problem, especially for transplantation, as such organoids will not be able to perform their physiological functions. In this study, we develop a method for generating murine kidney organoids with improved higher-order structure, through stages using chimaeras of ex-fetu and PSC-derived cells to a system that works entirely from embryonic stem cells. These organoids have nephrons organised around a single ureteric bud tree and also make vessels, with the endothelial network approaching podocytes.

AB - There is intense worldwide effort in generating kidney organoids from pluripotent stem cells, for research, for disease modelling and, perhaps, for making transplantable organs. Organoids generated from pluripotent stem cells (PSC) possess accurate micro-anatomy, but they lack higher-organization. This is a problem, especially for transplantation, as such organoids will not be able to perform their physiological functions. In this study, we develop a method for generating murine kidney organoids with improved higher-order structure, through stages using chimaeras of ex-fetu and PSC-derived cells to a system that works entirely from embryonic stem cells. These organoids have nephrons organised around a single ureteric bud tree and also make vessels, with the endothelial network approaching podocytes.

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Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells

Abstract

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Projects

Advancing renal tissue engineering: equipping tissue-engineered kidneys with a ureter

Advancing construction of human induced pluripotent stem cell (iPSC)-derived kidneys from current crude organoids to making anatomically realistic mini-organs.

SynthSys-Mammalian: Edinburgh Mammalian Synthetic Biology Research Centre

Cite this