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Immunoisolation effect of polyvinyl alcohol (PVA) macroencapsulated islets in type 1 diabetes therapy

机译:聚乙烯醇(PVA)大胶囊化胰岛在1型糖尿病治疗中的免疫隔离作用

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摘要

Islet transplantation has shown great success in the treatment of type 1 diabetes since the Edmonton protocol was established. However, it still has two major problems to overcome: the lack of organ donors and the side effects of immunosuppression. Encapsulated islets have emerged as a potential option for islet transplantation because it can, at least partly, overcome these two problems. Wistar rat islets suspended in 3% polyvinyl alcohol (PVA) hydrogel were frozen-thawed to make macroencapsulated islets (MEIs). The recovery rate, insulin content, and morphological change in culture medium with/without fresh human plasma (FHP) were measured in MEIs and free islets in vitro. In vivo, MEIs of either Wistar or Lewis rats were transplanted into the peritoneal cavity of streptozotocin (STZ)-induced diabetic Lewis rats and nonfasting blood glucose (NFBG), body weight, and histological evaluations were processed. FHP destroyed rat free islets but did not affect the islet morphology, islet recovery rate, or insulin content of rat MEIs. The transplantation of MEIs decreased the NFBG level and prevented body weight loss without a significant difference between the donor strains. Insulin-positive islets were observed in PVA MEIs 24 weeks after allotransplantation. These results suggest that PVA MEIs may be used as a cure for type 1 diabetes.
机译:自建立埃德蒙顿协议以来,胰岛移植已在治疗1型糖尿病方面取得了巨大成功。然而,它仍需克服两个主要问题:缺乏器官供体和免疫抑制的副作用。封装的胰岛已经成为胰岛移植的潜在选择,因为它可以至少部分地克服这两个问题。将悬浮在3%聚乙烯醇(PVA)水凝胶中的Wistar大鼠胰岛冷冻融化,制成大胶囊化胰岛(MEIs)。在MEIs和游离胰岛中,在有/无新鲜人血浆(FHP)的情况下测量培养基中的回收率,胰岛素含量和形态变化。在体内,将Wistar或Lewis大鼠的MEIs移植到链脲佐菌素(STZ)诱导的糖尿病Lewis大鼠的腹膜腔中,并进行非禁食血糖(NFBG),体重和组织学评估。 FHP破坏了大鼠的游离胰岛,但不影响大鼠MEI的胰岛形态,胰岛恢复率或胰岛素含量。 MEIs的移植降低了NFBG水平并防止了体重减轻,而供体之间没有显着差异。同种异体移植后24周,在PVA MEI中观察到胰岛素阳性胰岛。这些结果表明,PVA MEI可以用作1型糖尿病的治疗方法。

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