Duvivier-Kali Valérie F, Omer Abdulkadir, Lopez-Avalos Maria D, O'Neil John J, Weir Gordon C
Diabetes and Obesity Unit, Sanofi Synthelabo, Rueil-Malmaison, France.
Am J Transplant. 2004 Dec;4(12):1991-2000. doi: 10.1111/j.1600-6143.2004.00628.x.
The aim of this study was to assess the capacity of simple alginate capsules to protect adult pig islets in a model of xenotransplantation. Adult pig islets were microencapsulated in alginate, with either single alginate coats (SAC) or double alginate coats (DAC), and transplanted into the streptozotocin-induced diabetic B6AF1 mice. Normalization of glucose levels was associated with an improvement of the glucose clearance during intravenous glucose tolerance tests. After explantation, all mice became hyperglycemic, demonstrating the efficacy of the encapsulated pig islets. Explanted capsules were mainly free of fibrotic reaction and encapsulated islets were still functional, responding to glucose stimulation with a 10-fold increase in insulin secretion. However, a significant decrease in the insulin content and insulin responses to glucose was observed for encapsulated islets explanted from hyperglycemic mice. An immune response of both IgG and IgM subtypes was detectable after transplantation. Interestingly, there were more newly formed antibodies in the serum of mice transplanted with SAC capsules than in the serum of mice transplanted with DAC capsules. In conclusion, alginate capsules can prolong the survival of adult pig islets transplanted into diabetic mice for up to 190 days, even in the presence of an antibody response.
本研究的目的是在异种移植模型中评估简单藻酸盐胶囊保护成年猪胰岛的能力。成年猪胰岛被微囊化在藻酸盐中，采用单层藻酸盐包衣（SAC）或双层藻酸盐包衣（DAC），并移植到链脲佐菌素诱导的糖尿病B6AF1小鼠体内。静脉葡萄糖耐量试验期间，血糖水平正常化与葡萄糖清除率的改善相关。移植后，所有小鼠均出现高血糖，证明了包封的猪胰岛的有效性。移植后的胶囊主要没有纤维化反应，包封的胰岛仍然具有功能，对葡萄糖刺激的胰岛素分泌增加了10倍。然而，从高血糖小鼠体内取出的包封胰岛的胰岛素含量和对葡萄糖的胰岛素反应显著降低。移植后可检测到IgG和IgM亚型的免疫反应。有趣的是，移植SAC胶囊的小鼠血清中新生抗体比移植DAC胶囊的小鼠血清中更多。总之，即使存在抗体反应，藻酸盐胶囊也可以将移植到糖尿病小鼠体内的成年猪胰岛的存活时间延长至190天。
