Alginate Macroencapsulation of Pig Islets Allows Correction of Streptozotocin-Induced Diabetes in Primates up to 6 Months Without Immunosuppression
Alginate Macroencapsulation of Pig Islets Allows Correction of Streptozotocin-Induced Diabetes in Primates up to 6 Months Without Immunosuppression
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DOI：
10.1097/tp.0b013e3181f6e267
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发表时间：
2010-11-27
期刊：
影响因子：
6.2
通讯作者：
Gianello, Pierre
中科院分区：
文献类型：
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作者：
Dufrane, Denis;Goebbels, Rose-Marie;Gianello, Pierre
背景本研究评估了藻酸盐包封的胰岛在猪到灵长类动物模型中逆转糖尿病的能力。将成年猪胰岛包封在植入糖尿病灵长类动物肾包膜下的微胶囊中（n = 4）或皮下巨装置中（n = 5）。观察空腹血糖（FBG）、胰岛素、猪C肽、糖化血红蛋白（HbA 1C）以及细胞和体液反应。未包封的猪胰岛在7天内被排斥。微囊化猪胰岛移植于肾包膜下后2周内，仅观察到一过性FBG降低。皮下移植宏器械后，5只动物的糖尿病最多矫正6个月：FBG低于107 mg/dL，HbA 1C为8% +/-1.4%。在第一次移植物功能障碍（HbA 1C>= 13）后25 - 35周，5只动物中的2只接受了新的宏观器械，这些动物的糖尿病再控制了18周。虽然一个强大的体液反应引起移植后的包囊胰岛，总的不渗透性的藻酸盐3%重量/体积的IgG被证明之前和长达20周后移植的皮下macrodevices。猪胰岛封装在皮下macrodevice可以控制糖尿病长达6个月，没有免疫抑制。
Background. This study assessed the capacity of alginate-encapsulated islets to reverse diabetes in a pig-to-primate model.Methods. Adult pig islets were encapsulated in microcapsules implanted under the kidney capsule (n = 4) or in a subcutaneous macrodevice (n = 5) in diabetic primates. Fasting blood glucose (FBG), insulin, porcine C-peptide, glycosylated hemoglobin (HbA1C), and cellular and humoral responses were followed.Results. Nonencapsulated pig islets were rejected within 7 days. A transient decrease of FBG was observed only during the 2 weeks after microencapsulated pig islet implantation under the kidney capsule. After subcutaneous transplantation of a macrodevice, diabetes was corrected up to a maximum of 6 months in five animals: FBG less than 107 mg/dL and HbA1C at 8% +/- 1.4%. Two of the five animals received a new macrodevice between 25 and 35 weeks after the first graft dysfunction (HbA1C >= 13), and diabetes was controlled for an additional 18 weeks in these animals. Although a strong humoral response was elicited after transplantation of encapsulated islets, a total impermeability of alginate 3% wt/vol to IgG was demonstrated before and up to 20 weeks after transplantation of the subcutaneous macrodevice.Conclusions. Pig islets encapsulated in a subcutaneous macrodevice can control diabetes up to 6 months without immunosuppression.