Dufrane Denis, Goebbels Rose-Marie, Saliez Alain, Guiot Yves, Gianello Pierre
Laboratory of Experimental Surgery, Université catholique de Louvain, Faculté de Médecine, and Department of Pathology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Transplantation. 2006 May 15;81(9):1345-53. doi: 10.1097/01.tp.0000208610.75997.20.
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 primates.
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 implantation.
Nonencapsulated 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 response.
Optimal alginate encapsulation significantly prolonged adult pig islet survival into primates for up to 6 months, even in the presence of antibody response.
猪胰岛异种移植仍与强烈的体液和细胞异种免疫反应相关。本研究的目的是评估在灵长类动物中移植后藻酸盐包封的猪胰岛的长期生物相容性。
将在最佳条件下（n = 7）或未在最佳条件下（n = 5）用藻酸盐包封的成年猪胰岛移植到非糖尿病食蟹猴肾包膜下。另外的灵长类动物接受空胶囊（n = 1）和未包封的猪胰岛（n = 2）作为对照。在植入后长达6个月检查胶囊完整性、细胞过度生长、猪胰岛存活、猪C肽和抗猪IgM/IgG抗体。
未包封的胰岛和包封在非最佳胶囊中的胰岛迅速被破坏。在7只接受完美包封的猪胰岛的灵长类动物中，部分胰岛在植入后长达6个月存活，无需免疫抑制。1个月后在71%的动物中检测到猪C肽。大多数移植物（86%）完整，完全没有细胞过度生长或胶囊纤维化。在135天（n = 2/2）和180天（n = 2/3）后取出的胶囊显示有残余胰岛素含量和对葡萄糖刺激的反应（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。
即使存在抗体反应，最佳的藻酸盐包封也能显著延长成年猪胰岛在灵长类动物中的存活时间长达6个月。
