CLINICAL TRIALS ON HUMAN ISLET TRANSPLANTATION

人类胰岛移植的主要目的 I型胰岛素依赖型糖尿病（IDDM）是指 确定是否移植分离的、纯化的、成年的 人类胰岛可以消除对胰岛素治疗的需要。 最近 分离和纯化方法的改进 来自尸体捐赠的人胰腺的人胰岛提供了 持续高产70-95%纯人类胰岛， 50-100单位的胰岛素。 这些胰岛适当地响应于 体外葡萄糖激发，可成功移植 变成裸鼠 研究还表明，人类胰岛 在室温下培养7天后仍能存活 这可以降低它们被排斥的可能性。 因此， 改进的人类胰岛制备现在可用于测试， I型糖尿病患者。 本申请提出（1）在局部麻醉下进行移植， 将室温培养的胰岛植入患者的门静脉 患有I型胰岛素依赖型糖尿病20年， 并发症最少。 这些患者将接受 强的松、硫唑嘌呤和环孢素治疗12个月。 所有 那时停止注射胰岛素的患者 去除免疫抑制以确定 短暂免疫抑制和低温联合 培养将允许改变的胰岛长期植入， 已经在动物实验中得到证实。 它建议（2）移植 纯化的人胰岛通过门户网站进入I型胰岛素依赖型糖尿病 已经接受肾移植的患者， 基础免疫抑制 肾包膜下部位也将 通过移植来自相同培养物的培养2天的胰岛来检查 作为肾移植的供体 第三项研究将是（3） 移植冷冻保存的人胰岛以确定可行性 为将来的临床试验储存人类胰岛。 这些建议的研究结果移植纯化 将人类胰岛移植到不同的糖尿病患者群体中， 确定考虑胰岛移植作为一种 用于临床治疗I型IDDM患者的方法。

The primary objective of human islet transplantation into patients with Type I, Insulin Dependent Diabetes Mellitus (IDDM) is to determine whether the transplantation of isolated, purified, adult human islets can eliminate the need for insulin therapy. Recent improvements in the methods of isolation and purification of human islets from cadaver donated human pancreas have provided consistently high yields of 70-95% pure human islets that contain 50-100 units of insulin. These islets respond appropriately to a glucose challenge in vitro and can be successfully transplanted into nude mice. It has also been demonstrated that human islets remain viable after seven days of culture at room temperature which may reduce their potential for rejection. Thus, a markedly improved human islet preparation is now available to test in patients with Type I IDDM. This application proposes to (1) transplant under local anesthesia, room temperature-cultured islets into the portal vein of patients with type I IDDM who have had their disease for 20 years and have minimal complications. These patients will receive prednisone, azathioprine and cyclosporine for 12 months. All patients off insulin at that time will have their immunosuppression removed to determine whether the combination of transient immunosuppression and low temperature culture will permit long term engraftment of the altered islets as has been shown in animal studies. It proposed to (2) transplant purified human islets via the portal view into Type I IDDM patients who have already received a kidney transplant and are on basal immunosuppression. The renal subcapsular site will also be examined by transplanting 2 day cultured islets from the same donor as a kidney allograft. The third study will be to (3) transplant cryopreserved human islets to determine the feasibility of islet banking human islets for future clinical trials. The results of these proposed studies of transplanting purified human islets into different groups of patients with diabetes should determine the potential of considering islet transplantation as a method for clinical treatment of patients with Type I IDDM.