RESULTS OF OUR 1ST 9 INTRAPORTAL ISLET ALLOGRAFTS IN TYPE-1, INSULIN-DEPENDENT DIABETIC-PATIENTS
RESULTS OF OUR 1ST 9 INTRAPORTAL ISLET ALLOGRAFTS IN TYPE-1, INSULIN-DEPENDENT DIABETIC-PATIENTS
复制标题
DOI：
10.1097/00007890-199101000-00012
复制
发表时间：
1991-01-01
期刊：
影响因子：
6.2
通讯作者：
FLYE, MW
中科院分区：
文献类型：
--
作者：
SCHARP, DW;LACY, PE;FLYE, MW
随着门脉内胰岛移植到1型糖尿病患者体内后首次显示胰岛素独立，临床胰岛移植的新纪元将开始。这份报告提供了我们的临床胰岛移植的初步经验，总共有9次连续的门静脉胰岛移植在7例糖尿病患者中。前三个移植是在非肾功能衰竭糖尿病患者(NRFI)中完成的，移植的胰岛为6319+/-2173个/kg体重，胰岛取自单个胰腺，在24℃下培养7天。强的松、硫唑嘌呤和环孢素在移植前开始使用。虽然所有三名受者在移植后都表现出C肽功能，但三名受者在2周后都拒绝了移植。5天的OKT3治疗未能恢复超过10%的排斥胰岛移植物。然后，研究转移到现有的肾移植受者(EKI)，维持他们的基础免疫抑制，同时向受者添加7天的明尼苏达抗淋巴球蛋白(MALG)，使用来自单一捐赠者的胰岛，这些胰岛在24℃培养了7天。平均有6161+/-911个胰岛移植到3个EKI受体体内。这三人都有移植后的C肽反应，但没有人实现胰岛素独立。虽然第一个患者在移植后2周拒绝了他的移植，但两名受者在移植后10个月表现出长期的胰岛功能。潜伏期激发试验显示C-肽有反应性，但延迟模式提示移植的胰岛质量不足。接下来的三个肾移植受者从一个以上的供体胰腺获得胰岛，平均每公斤体重13,916+/-556个胰岛。其中第一个是第一个在移植后第10天到第25天实现胰岛素独立的人，当时她似乎出现了排斥反应。第二组和第三组接受来自多个供体的胰岛再次移植，从单个供体获得部分胰岛功能。第一个接受三重免疫抑制的患者在184天后表现出长期部分功能，但不是胰岛素依赖。使用强的松和硫唑嘌呤的第三名患者在培养7天后接受一半胰岛移植，另一半患者在7天培养结合冷冻保存后接受胰岛移植。他在移植后154天内继续表现出胰岛素的独立性，糖化血红蛋白值为5.6%。激发试验数据显示，移植后4个月的刺激C-肽总反应率为155 Rho-mol/ml，而正常对照组(NC)为148+/-12 Rho-mol/ml，接受三重免疫抑制的非糖尿病肾移植受者为425 Rho-mol/ml。这些结果证明了胰岛移植后1型患者实现胰岛素独立的可行性，并证明了继续这些研究的合理性，以证明有多少胰岛移植受者可以在移植后多长时间内实现胰岛素独立。
With the first demonstration of insulin independence following intraportal islet transplantation into a patient with type 1 diabetes, a new era of clinical islet transplantation will begin. This report provides our initial experience of clinical islet transplantion with a total of nine consecutive portal vein islet trasplants in seven diabetic recipients. The first three transplants were done in nonrenal failure diabetics (NRFI) using 6319 +/- 2173 islets/kg body weight with islets processed from single pancreas and cultured for 7 days at 24-degrees-C. Prednisone, azathioprine, and cyclosporine were initiated prior to transplant. While all three recipients demonstrated C-peptide function posttransplant, all three rejected their grafts at 2 weeks. Five days of OKT3 treatment failed to recover more than 10% of their rejecting islet grafts. The studies were then shifted to established kidney transplant recipients (EKI) maintaining their basal immunosuppression while adding 7 days of Minnesota antilymphoblast globulin (MALG) to the recipient using islets from single donor pancreas that had been cultured for 7 days at 24-degrees-C. There were an average of 6161 +/- 911 islets transplanted intraportally into three EKI recipients. All three had C-peptide response from the transplant, but none achieved insulin independence. While the first patient rejected his graft at 2 weeks, two recipients demonstrated long-term islet function up to 10 months posttransplant. Sustacal challenge testing demonstrated C-peptide responsiveness, but in a delayed pattern suggesting insufficient islet mass had been transplanted. The next three kidney transplant recipients received islets from more than one donor pancreas averaging 13,916 +/- 556 islets/kg body weight. The first of these was the first to achieve insulin independence from 10 to day 25 posttransplant when she appeared to have a rejection episode. The second and third recipients were retransplanted with islets from multiple donors having achieved partial islet function from single pancreas donor. The first patient on triple immunosuppression is demonstrating long-term partial function at 184 days but is not insulin independent. The third patient on prednisone and azathioprine received one half his islets after 7-day culture and the other half after 7-day culture combined with cryopreservation. He is continuing to demonstrate insulin independence for 154 days posttransplant with a glycated hemoglobin value of 5.6%. Sustacal challenge data demonstrate a total stimulated C-peptide response of 155 rho-mol/ml at 4 months posttransplant compared with 148 +/- 12 rho-mol/ml for normal controls (NC) and 425 rho-mol/ml for nondiabetic, established kidney transplant recipients on triple immunosuppression. These results demonstrate the feasibility of achieving insulin independence in type 1 patients after islet transplantation and justify continuing these studies to document how many recipients of islet transplantation can achieve insulin independence for what duration posttransplant.