Transplantation of Dispersed Pancreatic Islet Tissue in Humans: Autografs and Allografts
Transplantation of Dispersed Pancreatic Islet Tissue in Humans: Autografs and Allografts
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人体分散胰岛组织移植：自体移植和同种异体移植
DOI：
10.2337/diab.29.1.s31
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发表时间：
1980
期刊：
影响因子：
7.7
通讯作者：
J. Najarian
中科院分区：
文献类型：
--
作者：
D. Sutherland;A. Matas;F. Goetz;J. Najarian
胰岛移植在动物身上是成功的，并有望作为糖尿病患者的内分泌替代疗法，但在糖尿病患者的临床应用一直很困难。我们通过将分散的胰岛组织自体移植到门静脉中，在三名慢性胰腺炎患者中显示了人类胰岛移植的技术可行性，这些患者接受了近全(97%)胰腺切除，并伴有丧失能力的顽固性疼痛。在所有三名患者中，切除的胰腺都被胶原酶消化分散，但没有努力净化胰岛。根据组织胰岛素含量判断，胰岛产量在24%到55%之间。第一位患者，在胰腺切除和胰岛自体移植后从未接受过胰岛素治疗，在3周时口服葡萄糖耐量试验正常，并保持正常血糖超过2年。在第二例患者中，组织学发现肝实质中有存活的胰岛。第三例患者在胰腺切除和自体胰岛移植后进行了3wk的高营养治疗，并在此期间需要胰岛素。在停止高营养和开始口服喂养后，患者停用胰岛素。虽然存在碳水化合物代谢异常，但患者在超过一年的时间内不需要胰岛素。7例糖尿病肾移植受者接受了以相同方法制备的分散胰岛组织的同种异体移植。没有患者被治愈，尽管有一些患者出现了短暂的胰岛功能证据-血清或尿液C-肽水平增加或外源性胰岛素需求量减少。虽然排斥反应可能是大多数失败的原因，但作为游离移植物的同种异体人胰岛组织移植在代谢上是低效的。在目前免疫抑制治疗的情况下，胰岛移植的主要作用可能是在不会发生排斥的情况下：作为一种自体移植，以避免良性疾病广泛胰腺切除术后糖尿病的发生。
Islet transplantation is successful in animals and holds considerable promise as endocrine replacement therapy for patients with diabetes mellitus, but clinical application to diabetic patients has been difficult. We have shown the technical feasibility of human islet transplantation by autotransplantation of dispersed pancreatic islet tissue into the portal vein in three patients with chronic pancreatitis and incapacitating, intractable pain who underwent near-total (>97%) pancreatectomy. In all three patients, the excised pancreas was dispersed by collagenase digestion, but no effort was made to purify the islets. Islet yield, as judged by tissue insulin content, ranged from 24 to 55%. The first patient, who never received insulin after the pancreatectomy and islet autotransplantation, had a normal oral glucose tolerance test by 3 wk and has remained normoglycemic for over 2 yr. In the second patient, viable islets were histologically identified in the liver parenchyma. The third patient was treated with hyperalimentation for 3 wk after the pancreatectomy and islet autotransplantation and, during this period, required insulin. After cessation of hyperalimentation and initiation of oral feedings, the patient was withdrawn from insulin. Although abnormalities of carbohydrate metabolism were present, the patient did not require insulin for more than 1 yr. Seven diabetic renal eliografi recipients have received allografts of dispersed pancreatic islet tissue prepared in the same way. No patients were cured of diabetes, although transient evidence of islet function —increase in serum or urinary C-peptide levels or decrease in exogenous insulin requirements— occurred in some. Although rejection was probably responsible for most of the failures, transplantation of allogeneic human islet tissue as a free graft is metabolically inefficient. With the current state of immunosuppressive therapy, the primary role of islet transplantation may be in a situation where rejection cannot occur: as an autograft to obviate the occurrence of diabetes after extensive pancreatectomy for benign disease.