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

自20年前引入胰腺和胰岛细胞移植以来，它已经改变了糖尿病患者的治疗方式。胰岛移植是通过将产生胰岛素的细胞(胰岛)从器官捐赠者捐赠的胰腺中分离出来，检查胰岛的健康状况，然后将它们注入接受移植的人的肝脏血液中。与全器官胰腺移植相比，胰岛移植是一种风险较低的手术，对于正在接受胰岛素治疗的糖尿病患者来说，它可能会改变生活，有时甚至是一种挽救生命的疗法，但他们对血糖何时降得太低失去了意识。全器官胰腺移植仍然非常有帮助，通常作为肾脏和胰腺联合移植的一部分，用于因糖尿病而肾功能衰竭的人。肾脏和胰腺联合移植可以极大地延长患者的生命长度，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，但仍然缺乏合适的胰腺器官进行移植。在我的项目中，我将通过使用新药来改善胰岛细胞移植和全器官胰腺移植的结果，在移植过程中阻止炎症和防止细胞损伤。我们的目标是改善接受此类移植的人的结局，同时通过减少受损程度太高而无法安全使用的胰腺器官的数量，增加可以进行移植的人数。我将研究几种改善这一点的方法，包括使用一台特殊的机器为捐赠者的胰腺器官提供必要的营养和它所需的氧气。我还将使用新开发的药物来阻止胰腺炎症，这些炎症可以添加到用于准备胰腺移植的液体中。如果成功，我的研究将改善正在接受胰岛移植或胰腺移植的糖尿病患者的生活，使细胞和器官在植入时变得更健康。我们还将通过改善现有胰腺器官的健康状况，增加可以进行移植的糖尿病患者的数量。

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.