A human slice model to understand the role of fibrosis in children with bladder exstrophy

人体切片模型了解纤维化在膀胱外翻儿童中的作用

• 批准号: MR/X030946/1
• 负责人: Navroop Singh Johal
• 金额: $ 62.58万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX030946%2F1
• 关键词: human; slice; model; understand; role

Bladder exstrophy is a condition in babies where the bladder and front of the abdomen fail to develop properly, which leaves the open bladder exposed on the front of the tummy at birth. Surgery for affected children is only available in Manchester or Great Ormond Street (GOS) in the UK but outcomes are poor, even with the best care in these specialist centres: many are permanently incontinent with frequent urine infections and have sexual dysfunction in later life. The applicant, Mr Johal, leads exstrophy surgery at GOS and has a unique research background with a PHD focussing on normal and abnormal function of the muscles in the bladder. He has shown that most of the expected bladder muscles are replaced by scar tissue in exstrophy. This occurs via a process called fibrosis, which is also implicated in many other conditions; hence there are a number of new drugs being developed to treat fibrosis which have not yet been tested in exstrophy. Part of the abnormal bladder is removed during routine exstrophy surgery, and this will be used by Mr Johal to test whether fibrosis can be stopped (or even reversed) by these drugs, in collaboration with Professor David Long (Institute of Child Health) who has successfully undertaken similar experiments in the kidney. Taken together, Mr Johal's unique background, access to exstrophy samples and drive to improve outcomes combined with support from Professor Long's innovative laboratory team, this is a timely opportunity to increase understanding of bladder exstrophy and test new therapies that may be used clinically in future.

膀胱外藻是婴儿的一种疾病，腹部的膀胱和前部无法正常发育，这使开放的膀胱在出生时暴露在腹部的前部。受影响儿童的手术仅在英国的曼彻斯特或大奥蒙德街（GOS）进行，但结局很差，即使在这些专业中心的医疗服务中最好的护理也是最好的护理：许多人在尿液中常见尿液感染，并且在以后的生活中具有性功能障碍。申请人Johal先生在GOS上领导外肌手术，并具有独特的研究背景，其博士学位侧重于膀胱中肌肉的正常和异常功能。他表明，大多数预期的膀胱肌肉都被外肌肉中的疤痕组织取代。这是通过称为纤维化的过程发生的，这也与许多其他条件有关。因此，有许多新药正在开发用于治疗纤维化，而这些药物尚未在杂菌中进行测试。在常规外部手术期间，将去除部分异常膀胱，Johal先生将使用这些药物与戴维·朗（David Long）教授（儿童健康研究所）合作测试这些药物是否可以停止（甚至逆转）纤维化，后者在肾脏中成功进行了类似的实验。乔哈尔（Johal）的独特背景，获得外肌肉样本的访问权以及改善结果的驱动力以及朗教授的创新实验室团队的支持，这是一个及时的机会，可以及时增加对膀胱外藻类的理解和测试将来可能在临床上可能使用的新疗法。