Reduction of early graft loss after intraportal porcine islet transplantation in monkeys
Reduction of early graft loss after intraportal porcine islet transplantation in monkeys
复制标题
DOI：
10.1097/01.tp.0000250680.36942.c6
复制
发表时间：
2007-01-27
期刊：
影响因子：
6.2
通讯作者：
Trucco, Massimo
中科院分区：
文献类型：
--
作者：
Rood, Pleunie P. M.;Bottino, Rita;Trucco, Massimo
背景。猪胰岛可能解决移植用人胰岛短缺的问题。在灵长类动物门静脉内输注猪胰岛后，许多胰岛因所谓的即时血液介导的炎症反应（IBMIR）而丢失。我们报告我们在IBMIR方面的经验。
方法。10只猴子接受了门静脉内猪胰岛移植。免疫抑制治疗采用常规药物（n = 3）或基于共刺激阻断（n = 7）。对8只猴子进行了针对IBMIR的特定治疗；另外2只猴子未接受此类治疗（第1组）。眼镜蛇毒因子完全抑制了4只猴子的补体活性（第2组），硫酸葡聚糖对4只猴子进行了抗凝（第3组）。通过监测血糖、胰岛素需求和猪C肽值来监测胰岛移植物功能。
结果。在既未接受眼镜蛇毒因子也未接受硫酸葡聚糖的猴子（第1组）中，严重低血糖以及需要输注葡萄糖表明胰岛迅速遭到破坏；C肽水平最初较低，且在最初5天内进一步降低。在第2组和第3组中，胰岛破坏明显减少，糖尿病也有所缓解。然而，当输注40,000 IEQ/kg时，5天内血糖正常状态消失，但在1例中输注80,000 IEQ/kg时，血糖正常状态更持久。我们观察到，即使C肽水平处于健康非糖尿病猪的正常范围内，也不足以维持猴子的血糖正常。
结论。尽管移植前补体耗竭或抗凝可显著减少猪胰岛异种移植物的丢失，但单独使用任何一种方法都不足以预防IBMIR。
Background. Pig islets constitute a possible resolution to the shortage of human islets for transplantation. After intraportal infusion of porcine islets in primates, many islets are lost through what has been termed the instant blood-mediated inflammatory reaction (IBMIR). We report on our experience with IBMIR.Methods. Ten monkeys underwent intraportal porcine islet transplantation. Immunosuppressive therapy was with conventional agents (n=3) or based on costimulation blockade (n=7). Treatment specific for IBMIR was administered in eight monkeys; two additional monkeys received no such therapy (group 1). Cobra venom factor completely inhibited complement activity in four (group 2) and dextran sulfate provided anticoagulation in four (group 3). Islet graft function was monitored by following blood glucose, insulin requirement, and porcine C-peptide values.Results. In monkeys that received neither cobra venom factor nor dextran sulfate (group 1), there was rapid destruction of islets indicated by severe hypoglycemia and the need for dextrose infusion; C-peptide levels were initially low and further reduction occurred within the first five days. In both groups 2 and 3, there was significantly less destruction of islets and some reversal of diabetes. However, when 40,000 IEQ/kg were infused, normoglycemia was lost within five days, but when 80,000 IEQ/kg were infused in one case, normoglycemia was more persistent. We observed that even when C-peptide levels were in the normal range for healthy nondiabetic pigs, these were not sufficient to maintain normoglycemia in the monkeys.Conclusions. Although pretransplantation complement depletion or anticoagulation reduces porcine islet xenograft loss significantly, neither alone is sufficient to prevent IBMIR.