Vascularized composite islet-kidney transplantation in a miniature swine model.
Vascularized composite islet-kidney transplantation in a miniature swine model.
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小型猪模型中的血管化复合胰岛肾移植。
DOI：
10.1007/s12013-007-0027-4
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发表时间：
2007
影响因子：
2.6
通讯作者：
Sachs,DavidH
中科院分区：
文献类型：
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作者：
Vallabhajosyula,Prashanth;Griesemer,Adam;Yamada,Kazuhiko;Sachs,DavidH
本实验室以前的工作已经证明，同种异体胸腺组织作为复合血管化移植物的一部分的移植在植入和长期存活方面比单独移植胸腺组织或细胞要成功得多。我们随后将这一概念扩展到同种异体胰岛移植，比较胰岛细胞悬液与血管化复合胰岛-肾（IK）的存活率，所述血管化复合胰岛-肾（IK）通过在复合器官的同种异体移植之前2-3个月将自体胰岛注射到肾囊下制备。我们使用具有确定的MHC基因座的部分近交小型猪作为本研究的实验大动物，允许跨越特定MHC屏障的可重复移植。复合IK已经成功地移植通过轻微和完全MHC错配障碍，使用先前证明的治疗方案，以诱导长期耐受的肾脏同种异体移植物通过这些障碍。发现含有≥5000胰岛当量（IE）/kg受体体重的IK同种异体移植物能够逆转手术诱导的糖尿病，而通过门静脉或肾包膜下注射相当数量的纯化胰岛则不能。研究还针对制备自体“胸腺-胰岛-肾”（TIK），用于异种移植的潜在用途，其中胸腺组分旨在诱导耐受性，胰岛逆转糖尿病高血糖症。这两种类型的复合器官移植的使用可能最终适用于患有终末期糖尿病肾病的I型糖尿病患者的治疗。
Previous work from this laboratory has demonstrated that transplantation of allogeneic thymic tissue as part of a composite vascularized graft is far more successful in terms of both engraftment and long-term survival than transplantation of thymic tissue or cells alone. We have subsequently extended this concept to transplantation of allogeneic islets, comparing survival of islet cell suspensions to that of vascularized composite islet-kidneys (IK), prepared by injection of autologous islets underneath the renal capsule 2-3 months prior to allogeneic transplantation of the composite organ.We have utilized partially inbred miniature swine with defined MHC loci as the experimental large animals for this study, permitting reproducible transplantation across specific MHC barriers. Composite IK have been transplanted successfully across minor and full MHC mismatch barriers, using treatment regimens previously demonstrated to induce long-term tolerance of kidney allografts across these barriers. IK allografts containing ≥5000 islet equivalents (IE)/kg recipient body weight were found capable of reversing surgically induced diabetes, while injection of comparable numbers of purified islets via the portal vein or under the renal capsule did not. Studies are also being directed toward preparation of autologous “thymo-islet-kidneys” (TIK), for potential use as xenografts, in which the thymic component is intended to induce tolerance and the islets to reverse diabetic hyperglycemia. The use of both types of composite organ transplants may eventually be applicable to the treatment of type I diabetic patients suffering from end-stage diabetic nephropathy.