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Title: Composite- and entero- cystoplasty cell reactions and interactions in vivo
Author: Turner, Alexander M.
ISNI:       0000 0004 2718 8672
Awarding Body: University of York
Current Institution: University of York
Date of Award: 2008
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Management of end-stage bladder failure is complicated; the low capacity and non-compliant bladder increases urinary back-pressure to the kidneys, resulting in renal failure, and causes intractable incontinence. Once conservative and medical treatments have failed, bladder reconstructive surgery is offered. The gold standard treatment is enterocystoplasty, which involves augmentation of the bladder with enteric tissue. Although increasing capacity and compliance of the bladder, the procedure carries with it a number of serious complications attributable to exposure of the bowel mucosa to urine, chief among which is the risk of malignant transformation. The purpose of this thesis was to compare the current treatment with composite cystoplasty, a novel tissue-engineering technique designed to create a neobladder lined by urothelium. Patients who had undergone conventional enterocystoplasty provided biopsies of native and augmented segments of bladder for histological and immunohistochemical analysis, to allow the cellular consequences of the procedure to be assessed. For composite cystoplasty, urothelial cells were retrieved from pigs during open bladder biopsy. The cells were propagated in culture and induced to differentiate, defined by cell stratification, expression of immunohistochemical markers of terminal differentiation, elevated transepithelial resistance and low permeability. The cells were harvested as sheets, implanted onto vascularised, de-epithelialised porcine colon and the complex used to augment the urinary bladder. Assessment of human enterocystoplasty biopsies revealed significant morphological changes in the bowel, reflecting a protective response, with villous atrophy and increased goblet cell population. Areas of inflammation were evident in some patients. In the pigs, all bowel grafts were lined with urothelium, characterised by the expression of urothelium-specific markers. There was no evidence of scarring, colonic regrowth or metaplasia. It is proposed that composite cystoplasty can lead to the rapid establishment of a urinary barrier in vivo which, by ensuring urothelial continuity throughout the bladder, will not be associated with the serious complications resulting from bowel mucosal exposure to urine.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available