ISLET TRANSPLANTATION IN NON-UREMIC DIABETIC PATIENTS

非尿毒症糖尿病患者的胰岛移植

• 批准号: 7604238
• 负责人: Dixon B Kaufman
• 金额: $ 1.14万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604238
• 关键词: ISLET; TRANSPLANTATION; NON; UREMIC; DIABETIC

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The prevalence of type I diabetes in the United States is estimated to be about 800,000 individuals, and the incidence is approximately 30,000 new cases yearly. To date, there are no thoroughly preventative or curative measures available. The closest has been the Diabetes Control and Complications Trial that demonstrated intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy (worsening eye sight), nephropathy (kidney damage), and neuropathy (decreased sensation/changing sensation in hands/feet/arms/legs). The modality of beta cell (insulin producing cells in the pancreas) replacement by transplantation of the whole pancreas is the most successful method to control glycemia. Transplantation of the islets as free grafts extends the concept of beta cell replacement therapy for patients with type I diabetes. The attraction of islet transplantation compared to conventional pancreas transplantation is its minimal morbidity (severe side-effects) and relative little use of hospital resources. Beta cell replacement therapy by means of islet cell transplantation, when successful, reverses hyperglycemia and the need for exogenous insulin (insulin not produced by the person taking it). The primary barrier to successful human islet transplantation is rejection. The study of islet transplant rejection has revealed the importance of T-cells. However, T-cell mediated islet rejection is not the sole mechanism of islet graft injury post-transplantation. Non-specific host immune responses involving macrophages and macrophage-generated by-products are also detrimental to islet engraftment and function. Beta cell replacement therapy by means of islet cell transplantation, when successful, reverses hyperglycemia and the need for exogenous insulin therapy. Unfortunately, it is not routinely effective. Between January 1, 1990 and December 31, 1998, 267 cases of islet transplantation in type I diabetic recipients have been reported to the International Transplant Registry. Of these cases 245 were reported with one year follow-up and only 20 patients (8%) were insulin independent at one year. The vast majority (95%) of islet transplants have been performed in patients who are either simultaneously receiving a kidney transplant or who have already received one and thus are committed to receiving systemic immunosuppressive therapy. The goal of islet transplantation is to be able to apply it early enough in the course of the disease so that these secondary vascular complications are prevented. For this to occur, anti-rejection regimens must be devised that minimize organ specific side effects while providing substantial protection from rejection.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 据估计，美国 I 型糖尿病患病人数约为 800,000 人，每年新发病例约为 30,000 例。 迄今为止，还没有彻底的预防或治疗措施。 最接近的是糖尿病控制和并发症试验，该试验证明强化治疗可有效延迟糖尿病视网膜病变（视力恶化）、肾病（肾脏损伤）和神经病变（手/脚感觉减退/感觉改变/手臂/腿）。 通过整个胰腺移植来替代β细胞（胰腺中产生胰岛素的细胞）的方式是控制血糖最成功的方法。 作为游离移植物的胰岛移植扩展了针对 I 型糖尿病患者的 β 细胞替代疗法的概念。 与传统的胰腺移植相比，胰岛移植的吸引力在于其发病率极低（严重的副作用）并且对医院资源的使用相对较少。 通过胰岛细胞移植进行的β细胞替代疗法如果成功，可以逆转高血糖和对外源性胰岛素（胰岛素不是由服用者产生的）的需要。 人类胰岛移植成功的主要障碍是排斥反应。 胰岛移植排斥的研究揭示了 T 细胞的重要性。 然而，T细胞介导的胰岛排斥并不是移植后胰岛移植物损伤的唯一机制。 涉及巨噬细胞和巨噬细胞产生的副产物的非特异性宿主免疫反应也不利于胰岛移植和功能。 通过胰岛细胞移植进行的β细胞替代疗法如果成功，可以逆转高血糖和外源性胰岛素治疗的需要。 不幸的是，它通常并不有效。 1990年1月1日至1998年12月31日期间，国际移植登记处报告了267例I型糖尿病受者的胰岛移植病例。 在这些病例中，有 245 例进行了一年的随访，其中只有 20 例患者 (8%) 在一年内不再依赖胰岛素​​。 绝大多数（95%）的胰岛移植是在同时接受肾移植或已经接受肾移植并因此致力于接受全身免疫抑制治疗的患者中进行的。 胰岛移植的目标是能够在疾病过程中尽早应用，从而预防这些继发性血管并发症。 为此，必须设计抗排斥方案，最大限度地减少器官特异性副作用，同时提供实质性保护，防止排斥。