The Efficacy of an Immunoisolating Membrane System for Islet Xenotransplantation in Minipigs
The Efficacy of an Immunoisolating Membrane System for Islet Xenotransplantation in Minipigs
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DOI：
10.1371/journal.pone.0070150
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发表时间：
2013-08-01
期刊：
影响因子：
3.7
通讯作者：
Rotem, Avi
中科院分区：
文献类型：
--
作者：
Neufeld, Tova;Ludwig, Barbara;Rotem, Avi
在过去的十年中，开发一种保护异种胰岛的装置以治疗和潜在地治愈大型哺乳动物的糖尿病一直是一个重大挑战。鉴于供体短缺和大量符合胰岛移植条件的糖尿病患者，需要使用异种胰岛进行移植。然而，到目前为止，宿主对异种移植物的免疫反应性一直是使用猪胰岛的主要缺点。我们的研究证明了一种新型免疫保护膜的适用性，该膜允许在没有免疫抑制治疗的情况下成功地将大鼠胰岛异种移植到糖尿病小型猪中。将大鼠胰岛包裹在高度纯化的藻酸盐中，并整合到由多膜覆盖的塑料巨室中用于皮下移植。糖尿病Sinclair猪移植并随访长达90天。我们证明了移植物功能的持久性和正常免疫功能的恢复，而不需要免疫抑制治疗。这一概念可能为更广泛的胰岛替代疗法提供一种有吸引力的策略，该疗法将恢复糖尿病患者的内源性胰岛素分泌而不需要免疫抑制药物，甚至可能为安全利用异种胰岛供体开辟一条途径。
Developing a device that protects xenogeneic islets to allow treatment and potentially cure of diabetes in large mammals has been a major challenge in the past decade. Using xenogeneic islets for transplantation is required in light of donor shortage and the large number of diabetic patients that qualify for islet transplantation. Until now, however, host immunoreactivity against the xenogeneic graft has been a major drawback for the use of porcine islets. Our study demonstrates the applicability of a novel immunoprotective membrane that allows successful xenotransplantation of rat islets in diabetic minipigs without immunosuppressive therapy. Rat pancreatic islets were encapsulated in highly purified alginate and integrated into a plastic macrochamber covered by a poly-membrane for subcutaneous transplantation. Diabetic Sinclair pigs were transplanted and followed for up to 90 days. We demonstrated a persistent graft function and restoration of normoglycemia without the need for immunosuppressive therapy. This concept could potentially offer an attractive strategy for a more widespread islet replacement therapy that would restore endogenous insulin secretion in diabetic patients without the need for immunosuppressive drugs and may even open up an avenue for safe utilization of xenogeneic islet donors.