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Decellularization of Mouse Kidneys to Generate an Extracellular Matrix Gel for Human Induced Pluripotent Stem Cell Derived Renal Organoids

Nag, Sparshita; Boyd, Ashleigh S; (2023) Decellularization of Mouse Kidneys to Generate an Extracellular Matrix Gel for Human Induced Pluripotent Stem Cell Derived Renal Organoids. Organoids , 2 (1) pp. 66-78. 10.3390/organoids2010005. Green open access

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Abstract

Chronic Kidney Disease (CKD) is a major cause of morbidity and mortality characterized by progressive renal fibrosis, and in extreme cases, renal failure. Human CKD models that replicate the biological complexity of the kidney and CKD are lacking and will be invaluable in identifying drugs to revert and/or prevent fibrosis. To address this unmet need, we developed 3D renal organoids where human induced pluripotent stem cells (hiPSCs) were differentiated to renal progenitors within a renal extracellular matrix (rECM) gel, based on the premise that an rECM could recreate the renal niche to facilitate hiPSC-derived renal progenitor generation. We used mouse kidneys as a source of rECM and identified that superior detergent-mediated decellularization of mouse kidneys was achieved with a combination of 0.5% w/v Sodium Dodecyl Sulphate and 1% v/v Triton-X and mechanical agitation for 60 h. HiPSCs that underwent specification to become metanephric mesenchyme (MM) were subsequently cultured within the rECM gel and, notably, mesenchymal to epithelial transition (MET) was observed, as judged by expression of nephron markers K-cadherin, Nephrin and WT1. These data demonstrate a role for rECM gel in developing human renal organoids from hiPSCs, which will aid the further development of a human disease model for renal fibrosis.

Type: Article
Title: Decellularization of Mouse Kidneys to Generate an Extracellular Matrix Gel for Human Induced Pluripotent Stem Cell Derived Renal Organoids
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/organoids2010005
Publisher version: https://doi.org/10.3390/organoids2010005
Language: English
Additional information: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Keywords: decellularization; renal organoids; iPSCs; extracellular matrix; directed differentiation; mesenchymal to epithelial transition; CKD; fibrosis; disease modeling; kidney
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10168048
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