Hellerström C, Andersson A, Groth C G, Sandler S, Jansson L, Korsgren O, Swenne I, Petersson B, Tollemar J, Tydén G
Department of Medical Cell Biology, Uppsala University, Sweden.
Diabetes Care. 1988 Nov-Dec;11 Suppl 1:45-53.
Although transplantations of vascularized pancreas in diabetic patients show steadily improving results, the immediate operative risks and life-long immunosuppressive medication involved represent considerable disadvantages. Efforts are being made to develop simpler and safer methods of transplantation with isolated pancreatic islet grafts, e.g., isolated islets, fetal pancreas, or dispersed adult pancreas. Iso-, allo-, and xenografts of such preparations have been shown to reverse diabetes in animals. However, attempts to apply these techniques in clinical practice have remained largely unsuccessful, and major technical advances are needed before success is achieved. Attempts to use whole, segmented, or isolated islets from pancreatic grafts as a cure for diabetes in animals and in diabetic patients are reviewed. The importance to the graft's permanent function, of adequate preparation and storage of the graft, and of beta-cell growth and vascularization are reviewed. Various forms of immunomodulation by pretreatment of grafts in vitro have been employed in animal models of diabetes, but none of these have yet been employed with long-term success in humans. Recurrence of a specific autoimmune response toward the beta-cell in a spontaneously diabetic recipient is a potential mechanism for destruction of transplanted islet tissue.
尽管糖尿病患者的血管化胰腺移植效果在稳步改善,但手术的直接风险以及所需的终身免疫抑制药物治疗是相当大的不利因素。人们正在努力开发更简单、更安全的孤立胰岛移植方法,例如,孤立胰岛、胎儿胰腺或分散的成年胰腺。已证实此类制剂的同基因、异基因和异种移植能使动物糖尿病逆转。然而,将这些技术应用于临床实践的尝试大多未成功,在取得成功之前还需要重大的技术进步。本文综述了在动物和糖尿病患者中使用胰腺移植物的完整、分段或孤立胰岛治疗糖尿病的尝试。还综述了移植物的充分制备和储存、β细胞生长和血管形成对移植物永久功能的重要性。在糖尿病动物模型中已采用多种通过体外预处理移植物进行免疫调节的形式,但这些方法在人类中均未获得长期成功应用。自发性糖尿病受体对β细胞的特异性自身免疫反应复发是移植胰岛组织被破坏的潜在机制。