Transplantation of pancreatic islets contained in minimal volume microcapsules in diabetic high mammalians

Transplantation of pancreatic islets contained in minimal volume microcapsules in diabetic high mammalians
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DOI:
10.1111/j.1749-6632.1999.tb08506.x
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发表时间:
1999-01-01
期刊:
BIOARTIFICIAL ORGANS II: TECHNOLOGY, MEDICINE, AND MATERIALS
影响因子:
--
通讯作者:
Brunetti, P
Brunetti, P
中科院分区:
其他
文献类型:
--
作者:
Calafiore, R;Basta, G;Brunetti, P

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为了最大限度地减少与用于胰岛移植免疫分离的标准海藻酸盐微胶囊 (CSM) 尺寸过大(直径 600-800 mu)相关的技术问题,我们开发了两种新型最小体积、化学相同的胶囊原型 (MVC):1) 连贯微胶囊 (Chl) 和 2) 中等尺寸微胶囊(300-400 mu,MSM)。 Chi 将每个单独的胰岛包裹在薄薄的藻酸盐水凝胶铸件内,是通过乳化制备的,而 MSM 是通过特殊的微滴发生器雾化胰岛藻酸盐悬浮液而制成的。在移植到糖尿病啮齿动物中后,Chi 已显示出对同种异体和异种非不一致胰岛的免疫保护,并恢复正常血糖。在高等哺乳动物中,在亚治疗剂量下,CM 完全免疫保护同种异体胰岛移植物(猪→猪),但只能暂时保护异种移植物(狗→猪)。然后,我们使用 MSM 在患有自发性胰岛素依赖型糖尿病的狗的腹腔中免疫分离犬胰岛同种异体移植物。在三只移植的狗中,两只显示出随着胰岛素戒断,高血糖完全缓解。 MSM 可以代表腹膜免疫隔离胰岛移植的 CSM 和 CM 之间的中间解决方案。
To minimize technical problems relating to excessive size (600-800 mu in diameter) of standard alginate microcapsules (CSM) for pancreatic islet graft immunoisolation, we have developed two novel minimal volume, chemically Identical, capsule prototypes (MVC): 1) coherent microcapsules (Chl), and 2) medium-size microcapsules (300-400 mu, MSM). Chi, which envelop each individual islet within a thin alginate hydrogel cast, are prepared by emulsification, whereas MSM are made by atomizing the islet-alginate suspension through a special microdroplet generator. Upon graft into diabetic rodents, Chi have shown to immunoprotect both allo- and xenogeneic nondiscordant islets, and restored normoglycemia, In higher mammals, at subtherapeutic doses, CM fully immunoprotected islet allografts (pig-->pig), but only temporarily xenografts (dog-->pig). We then used MSM to immunoisolate canine islet allografts in the peritoneal cavity of dogs with spontaneous insulin-dependent diabetes, Of three grafted dogs, two showed full remission of hyperglycemia with insulin withdrawal. MSM could represent an intermediate solution between CSM and CM for peritoneal immunoisolated islet transplants.