Kynurenine-3-monooxygenase inhibition as a novel therapeutic strategy to enhance islet cell viability and improve outcomes of Islet Transplantation

胰腺和胰岛细胞移植自20年前引入以来，已经改变了糖尿病患者的治疗方法。胰岛移植是通过将产生胰岛素的细胞（胰岛）从器官捐赠者捐献的胰腺中分离出来，检查胰岛的健康状况，然后将它们注射到接受移植的人的肝脏血液中来完成的。胰岛移植比全器官胰腺移植的风险更低，对于使用胰岛素的糖尿病患者来说，胰岛移植可以改变他们的生活，有时甚至可以挽救他们的生命，因为他们已经失去了血糖过低的意识。全器官胰腺移植仍然非常有用，通常作为肾脏和胰腺联合移植的一部分，用于因糖尿病而肾脏衰竭的人。肾脏和胰腺联合移植可以显著延长患者的寿命，提高患者的生活质量。然而，尽管胰腺和胰岛移植取得了成功，但适合移植的胰腺器官仍然短缺。在我的项目中，我将研究通过使用在移植过程中阻断炎症和防止细胞损伤的新药来改善胰岛细胞移植和全器官胰腺移植的结果。我们的目标是改善接受这些移植的人的结果，同时通过减少胰腺器官的数量来增加可以接受移植的人数，因为胰腺器官受损太严重，无法安全使用。我将研究几种改善这种情况的方法，包括使用一种特殊的机器为捐赠的胰腺器官提供它所需的必需营养和氧气。我还将使用新开发的药物来阻止胰腺炎症，这种药物可以添加到用于准备胰腺移植的液体中。如果成功，我的研究将改善接受胰岛移植或胰腺移植的糖尿病患者的生活，使细胞和器官在移植时更健康。我们还将通过改善可用胰腺器官的健康状况，增加可以接受移植手术的糖尿病患者数量。

Pancreas and islet cell transplant has transformed the treatment of people with diabetes since it was introduced 20 years ago. Islet transplant is done by separating the insulin producing cells (islets) from the pancreas donated by an organ donor, checking the islets for health, and then injecting them into the liver bloodstream of the person getting the transplant. Islet transplant is a lower risk procedure than having a whole-organ pancreas transplant and can be a life-changing, and sometimes a life-saving therapy, for people with diabetes who are on insulin, but who have lost awareness of when their blood sugar goes too low. Whole-organ pancreas transplant is still very helpful, and is usually performed as part of a combined kidney and pancreas transplant for people whose kidneys have failed due to their diabetes. A combined kidney and pancreas transplant can dramatically increase the length and quality of someone's life. However, despite the success of pancreas and islet transplant there continues to be a shortage of suitable pancreas organs for transplant.In my project I am going to do research to improve the outcomes of islet cell transplant and whole-organ pancreas transplants by using new medicines that block inflammation and prevent cell damage during the transplant process. Our aim is to improve the outcomes for people getting one of these tranplants, but also to increase the number of people who can have a transplant, by reducing the number of pancreas organs that are too damaged to be safely used. I am going to research several ways of improving this, including using a special machine to provide the donor pancreas organ with essential nutrients and oxygen that it needs. I am also going to use newly developed medicines that block pancreas inflammation that can be added into the fluid that is used to prepare the pancreas for transplant. If successful, my research is going to improve the lives of people with diabetes who are having an islet transplant or a pancreas transplant, by making the cells and organs healthier when they are put in. We will also increase the number of people with diabetes that can have a transplant, by improving the health of the available pancreas organs.