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- W2953055967 abstract "Murine models describe a defined host/pathogen interaction for urinary tract infection, but human cell studies are scant. Although recent human urothelial organoid models are promising, none demonstrate long-term tolerance to urine, the natural substrate of the tissue and of the uropathogens that live there. We developed a novel human organoid from progenitor cells which demonstrates key structural hallmarks and biomarkers of the urothelium. After three weeks of transwell culture with 100% urine at the apical interface, the organoid stratified into multiple layers. The apical surface differentiated into enlarged and flattened umbrella-like cells bearing characteristic tight junctions, structures resembling asymmetric unit membrane plaques, and a glycosaminoglycan layer. The apical cells also expressed cytokeratin-20, a spatial feature of the mammalian urothelium. Urine itself was necessary for full development, and undifferentiated cells were urine-tolerant despite the lack of membrane plaques and a glycosaminoglycan layer. Infection with Enterococcus faecalis revealed the expected invasive outcome, including urothelial sloughing and the formation of intracellular colonies similar to those previously observed in patient cells. This new biomimetic model could help illuminate invasive behaviours of uropathogens, and serve as a reproducible test bed for disease formation, treatment and resolution in patients." @default.
- W2953055967 created "2019-06-27" @default.
- W2953055967 creator A5003815090 @default.
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- W2953055967 creator A5084359780 @default.
- W2953055967 creator A5030825373 @default.
- W2953055967 date "2018-01-19" @default.
- W2953055967 modified "2023-10-15" @default.
- W2953055967 title "A urine-dependent human urothelial organoid offers a potential alternative to rodent models of infection" @default.
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- W2953055967 doi "https://doi.org/10.1038/s41598-018-19690-7" @default.
- W2953055967 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5775255" @default.
- W2953055967 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29352171" @default.
- W2953055967 hasPublicationYear "2018" @default.
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