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Barrier-Forming Potential of Epithelial Cells from the Exstrophic Bladder

Hinley, Jennifer; Duke, Rosalind; Jinks, Jessica; Stahlschmidt, Jens; Keene, David; Cervellione, Raimondo M; Mushtaq, Imran; ... Southgate, Jennifer; + view all (2022) Barrier-Forming Potential of Epithelial Cells from the Exstrophic Bladder. The American Journal of Pathology , 192 (6) pp. 943-955. 10.1016/j.ajpath.2022.03.009. Green open access

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Abstract

Bladder exstrophy (BEX) is a rare developmental abnormality resulting in an open, exposed bladder plate. Although normal bladder urothelium is a mitotically quiescent barrier epithelium, histologic studies of BEX epithelia report squamous and proliferative changes that can persist beyond surgical closure. The current study examined whether patient-derived BEX epithelial cells in vitro were capable of generating a barrier-forming epithelium under permissive conditions. Epithelial cells isolated from 11 BEX samples, classified histologically as transitional (n = 6) or squamous (n = 5), were propagated in vitro. In conditions conducive to differentiated tight barrier formation by normal human urothelial cell cultures, 8 of 11 BEX lines developed transepithelial electrical resistances of more than 1000 Ω.cm2, with 3 squamous lines failing to generate tight barriers. An inverse relationship was found between expression of squamous KRT14 transcript and barrier development. Transcriptional drivers of urothelial differentiation PPARG, GATA3, and FOXA1 showed reduced expression in squamous BEX cultures. These findings implicate developmental interruption of urothelial transcriptional programming in the spectrum of transitional to squamous epithelial phenotypes found in BEX. Assessment of BEX epithelial phenotype may inform management and treatment strategies, for which distinction between reversible versus intractably squamous epithelium could identify patients at risk of medical complications or those who are most appropriate for reconstructive tissue engineering strategies.

Type: Article
Title: Barrier-Forming Potential of Epithelial Cells from the Exstrophic Bladder
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ajpath.2022.03.009
Publisher version: https://doi.org/10.1016/j.ajpath.2022.03.009
Language: English
Additional information: Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0).
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 Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10179096
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