Six-month survival of microencapsulated pig islets and alginate biocompatibility in primates: Proof of concept
Six-month survival of microencapsulated pig islets and alginate biocompatibility in primates: Proof of concept
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DOI：
10.1097/01.tp.0000208610.75997.20
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发表时间：
2006-05-15
期刊：
影响因子：
6.2
通讯作者：
Gianello, Pierre
中科院分区：
文献类型：
--
作者：
Dufrane, Denis;Goebbels, Rose-Marie;Gianello, Pierre
背景。猪胰岛异种移植仍然与强烈的体液和细胞异种免疫反应有关。本研究的目的是评估海藻酸盐封装的猪胰岛在灵长类动物移植后的长期生物相容性。将在最佳条件下 (n = 7) 或未在最佳条件下 (n = 5) 封装在藻酸盐中的成年猪胰岛移植到非糖尿病食蟹猴的肾被膜下。其他灵长类动物接受空胶囊 (n=1) 和未封装的猪胰岛 (n=2) 作为对照。植入后长达 6 个月检查包膜完整性、细胞过度生长、猪胰岛存活、猪 C 肽和抗猪 IgM/IgG 抗体。未封装的胰岛和封装在非最佳胶囊中的胰岛被迅速破坏。在七种接受完美封装的猪胰岛的灵长类动物中，部分胰岛在植入后在没有免疫抑制的情况下存活了长达 6 个月。 1 个月后，71% 的动物体内检测到猪 C 肽。大多数移植物（86%）完好无损，完全没有细胞过度生长或包膜纤维化。 135 (n=2/2) 和 180 (n=2/3) 天后，外植的胶囊显示出残留的胰岛素含量和对葡萄糖挑战的反应（刺激指数为 2.2）。尽管引发了抗猪 IgG 体液反应，但仍获得了部分胰岛存活结论。即使存在抗体反应，最佳的藻酸盐封装也可显着延长成年猪胰岛在灵长类动物中的存活时间长达 6 个月。
Background. Pig islets xenotransplantation remains associated with a strong humoral and cellular xenogeneic immune responses. The aim of this study was to assess the long-term biocompatibility of alginate encapsulated pig islets after transplantation in primatesMethods. Adult pig islets encapsulated in alginate under optimal conditions (n = 7) or not (n = 5) were transplanted under the kidney capsule of nondiabetic Cynomolgus maccacus. Additional primates received empty capsules (n=1) and nonencapsulated, pig islets (n=2) as controls. Capsule integrity, cellular overgrowth, pig islet survival, porcine C-peptide and anti-pig IgM/IgG antibodies were examined up to 6 months after implantationResults. Nonericapsulated islets and islets encapsulated in nonoptimal capsules were rapidly destroyed. In seven primates receiving perfectly encapsulated pig islets, part of the islets survived up to 6 months after implantation without immunosuppression. Porcine C-peptide was detected after 1 month in 71% of the animals. The majority of grafts (86%) were intact and completely free of cellular overgrowth or capsule fibrosis. Explanted capsules, after 135 (n=2/2) and 180 (n=2/3) days, demonstrated residual insulin content and responses to glucose challenge (stimulation index of 2.2). Partial islet survival was obtained despite an elicited anti-pig IgG humoral responseConclusions. Optimal alginate encapsulation significantly prolonged adult pig islet survival into primates for up to 6 months, even in the presence of antibody response.