Autologous cell engineered bladder augmentation

在英国，大约有300万人经历过尿失禁，NHS每年的管理费用超过5亿英镑。它可以由先天性异常引起，如胎儿膀胱发育不全（膀胱外溢），也可以由后天条件引起，如膀胱的顺应性丧失（神经性膀胱）或膀胱癌。对于终末期膀胱疾病，最常用的增加或替换膀胱的外科手术包括纳入一个血管化的、重新配置的肠段（肠囊成形术）。虽然这种手术可以控制尿失禁并提高生活质量，但它通常与严重的并发症有关，包括感染、粘液产生和结石形成，以及可能的长期癌症风险。这些并发症主要是由于肠黏膜在结构和生理上与长期暴露于尿液不相容。已经提出了许多膀胱工程策略，这些策略通常依赖于将天然或合成的生物材料结合到膀胱中，这些材料可能会或不会与来自患者（自体）的细胞预培养。尽管有一些高调的报道，但很少有证据表明膀胱组织工程可以达到与当前外科技术相当的功能结果，并且仍然存在未满足的临床需求。该项目的目的是通过自体细胞工程策略为患者提供功能性膀胱重建。该项目将汇集干细胞和泌尿学（ICH、GOSH、Evelina London Children’s Hospital）、尿路上皮细胞生物学和膀胱组织工程学（约克大学）的专业知识，目的是开发一种膀胱重建的新技术，该技术将首先适用于膀胱外翻患者，但最终将扩展到任何需要膀胱增强的儿科或成人患者。项目将分为以下几个阶段：1。准备一个与移植相关的人上皮细胞库，用于复合膀胱成形术的评估。使用复合膀胱成形术将人上皮细胞移植到免疫抑制的猪体内，并在牺牲前监测3 - 6个月的功能。主要结局指标将是：以生存期衡量的安全性；通过新膀胱的容量和顺应性来衡量疗效。这一阶段的次要措施将包括：手术发病率、死后大体解剖和增强和原生粘膜的免疫组织学分析

Some 3 million people in the UK experience incontinence and the cost of management is over £500 million per annum to the NHS. It can be caused by both congenital anomalies, such as a failure of the bladder in the fetus to form (bladder exstrophy), and acquired conditions such as a loss of the compliance of the bladder (neuropathic bladder) or bladder cancer. For end-stage bladder disease, the most commonly performed surgical procedure to augment or replace the bladder involves incorporating a vascularised, reconfigured segment of bowel (enterocystoplasty). Although this procedure can provide continence and enhance quality of life, it is commonly associated with serious complications, including infections, mucus production and stone formation, and a possible long-term risk of cancer. These complications are primarily due to the fact that bowel mucosa is structurally and physiologically incompatible with the long-term exposure to urine. A number of bladder engineering strategies have been proposed and typically, these rely upon the incorporation of a natural or synthetic biomaterial into the bladder, which may or not be pre-cultured with cells derived from the patient (autologous). Despite some high profile reports, there is little evidence that bladder tissue engineering can yet achieve a functional outcome equivalent to current surgical techniques, and there remains an unmet clinical need. The aim of this programme is to deliver functional bladder reconstruction to patients through an autologous cell engineering strategy. This project will bring together expertise in stem cells and urology (ICH, GOSH, Evelina London Children's Hospital) with urothelial cell biology and bladder tissue engineering (University of York) with the purpose of developing a novel technique for bladder reconstruction that will be applicable in the first instance to patients with bladder exstrophy, but eventually extended to any paediatric or adult patient requiring bladder augmentation. The stages of the project will be to: 1. Prepare a bank of transplant-relevant human epithelial cells for assessment in composite cystoplasty.2. Transplant human epithelial cells into immunosuppressed pigs using the composite cystoplasty procedure and monitor function for 3 & 6 months before sacrifice. Principal outcome measures will be: safety as measured by survival; efficacy as measured by capacity and compliance of the neo-bladder. Secondary measures for this phase will include: surgical morbidity, post-mortem gross anatomy and immunohistological analysis of both the augmented and native mucosa