Lambrigts D, Sachs D H, Cooper D K
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
Transplantation. 1998 Sep 15;66(5):547-61. doi: 10.1097/00007890-199809150-00001.
The pig-to-primate model is increasingly being utilized as the final preclinical means of assessing therapeutic strategies aimed at allowing discordant xenotransplantation. We review here the world experience of both pig-to-human and pig-to-nonhuman primate organ transplantation. Eight whole organ transplants using discordant mammalian donors have been carried out in human recipients; only one patient was reported (in 1923) to have survived for longer than 72 hr. Therapeutic approaches in the experimental laboratory setting have included pharmacologic immunosuppression, antibody and/or complement depletion or inhibition, the use of pig organs transgenic for human complement regulatory proteins, and conditioning regimens aimed at inducing a state of tolerance or specific immunologic hyporesponsiveness. The greatest success to date has been obtained with methods that inhibit complement-mediated injury, either by the administration of cobra venom factor or soluble complement receptor I to the recipient (with organ survival up to 6 weeks) or by the use of donor organs transgenic for human decay-accelerating factor (with organ survival up to 2 months). The future of xenotransplantation may lie in the judicious combination of current approaches.
猪到灵长类动物模型正越来越多地被用作评估旨在实现不协调性异种移植的治疗策略的最终临床前手段。我们在此回顾猪到人类和猪到非人类灵长类动物器官移植的全球经验。八例使用不协调性哺乳动物供体的全器官移植已在人类受者中进行；据报道，只有一名患者（在1923年）存活超过72小时。实验实验室环境中的治疗方法包括药理学免疫抑制、抗体和/或补体耗竭或抑制、使用转人补体调节蛋白基因的猪器官，以及旨在诱导耐受状态或特异性免疫低反应性的预处理方案。迄今为止，通过抑制补体介导的损伤的方法取得了最大的成功，方法包括向受者施用眼镜蛇毒因子或可溶性补体受体I（器官存活长达6周），或使用转人衰变加速因子基因的供体器官（器官存活长达2个月）。异种移植的未来可能在于当前方法的明智组合。
