CLINICAL TRIALS ON HUMAN ISLET TRANSPLANTATION

人胰岛移植的首要目标 对于I型，胰岛素依赖型糖尿病(IDDM) 确定分离、纯化、成体移植 人类的胰岛可以消除对胰岛素治疗的需要。近期 细菌分离纯化方法的改进 来自身体捐赠的人胰腺的人胰岛提供了 含有70%-95%纯人胰岛的产量一直很高 50-100个单位的胰岛素。这些胰岛适当地对 葡萄糖在体外的挑战并可成功移植 变成裸鼠。也有证据表明，人类的胰岛 在室温下培养7天后仍能存活 这可能会降低他们被排斥的可能性。因此，一个明显的 改进的人类胰岛制剂现在可以在 I型IDDM患者。 本申请建议(1)在局部麻醉下进行移植， 患者门静脉内常温培养的胰岛 患有I型糖尿病的人，他们已经患病20年， 并发症最小。这些患者将会收到 强的松、硫唑嘌呤和环孢素治疗12个月。全 届时停用胰岛素的患者将有他们的 去除免疫抑制以确定是否 一过性免疫抑制与低温的结合 培养将允许长期植入改变的胰岛作为 已经在动物研究中得到了证实。它建议(2)移植 经门脉切面纯化的人胰岛进入I型IDDM 已经接受肾移植并正在接受肾移植的患者 基础免疫抑制。肾被膜下部位也将是 通过移植培养2天的胰岛进行检查 供者作为同种异体肾移植。第三项研究将是(3) 移植深低温保存的人胰岛的可行性 用于未来临床试验的人类胰岛银行。 这些拟议的移栽研究结果纯净化 人类胰岛进入不同人群的糖尿病患者应 确定将胰岛移植作为一种 1型胰岛素依赖型糖尿病临床治疗方法。

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.