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

膀胱外翻是一种婴儿膀胱和腹部前部发育不正常的情况，这使得出生时开放的膀胱暴露在腹部前部。受影响的儿童只有在英国的曼彻斯特或大奥蒙德街（GOS）才能接受手术，但即使在这些专业中心得到最好的护理，结果也很差：许多人永久失禁，经常尿感染，并在以后的生活中出现性功能障碍。申请人Johal先生在GOS领导外翻手术，并拥有独特的研究背景，博士学位专注于膀胱肌肉的正常和异常功能。他已经证明，大多数预期的膀胱肌肉在外翻时被疤痕组织所取代。这是通过一个叫做纤维化的过程发生的，这个过程也与许多其他疾病有关；因此，有许多治疗纤维化的新药正在开发中，但尚未在外生性纤维化中进行试验。在常规的膀胱外翻手术中，部分异常膀胱被切除，Johal先生将用这些药物来测试纤维化是否可以停止（甚至逆转），他与大卫·朗教授（儿童健康研究所）合作，他已经成功地在肾脏上进行了类似的实验。综合而言，Johal先生的独特背景、获取膀胱外翻样本的途径以及在Long教授创新实验室团队的支持下改善结果的动力，这是一个及时的机会，可以增加对膀胱外翻的了解，并测试未来可能用于临床的新疗法。

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.