Tseng Yau-Lin, Kuwaki Kenji, Dor Frank J M F, Shimizu Akira, Houser Stuart, Hisashi Yosuke, Yamada Kazuhiko, Robson Simon C, Awwad Michel, Schuurman Henk-Jan, Sachs David H, Cooper David K C
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Transplantation. 2005 Nov 27;80(10):1493-500. doi: 10.1097/01.tp.0000181397.41143.fa.
The recent generation of alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs has allowed investigation of the survival of GalT-KO pig organs in nonhuman primates.
Heterotopic heart transplantation from GalT-KO pigs was carried out in baboons (n=8) using a human antihuman CD154 monoclonal antibody-based immunosuppressive regimen.
In six of the eight cases, graft survival extended to between approximately 2 and 6 months. All grafts developed thrombotic microangiopathy (TM). In particular, the clinical course of one baboon in which the graft functioned for 179 days is summarized. This baboon received aspirin (40 mg on alternate days) from day 4 in addition to heparin, which may have been a factor in the delay of onset and progression of TM and in prolonged graft survival. Maintenance therapy with anti-CD154 mAb, mycophenolate mofetil, and methylprednisolone was associated with persistently low numbers of CD3CD4 and CD3CD8 cells. Despite persisting depletion of these cells, no infectious complications occurred.
It remains to be established whether TM is related to a very low level of natural preformed or T-cell-induced antibody deposition on the graft, inducing endothelial activation and injury, or to molecular incompatibilities in the coagulation mechanisms between pig and baboon, or to both. However, function of a pig organ in a baboon for a period approaching six months, which has not been reported previously, lends encouragement that the barriers to xenotransplantation will eventually be overcome.
最近一代的α1,3-半乳糖基转移酶基因敲除（GalT-KO）猪使得研究GalT-KO猪器官在非人类灵长类动物中的存活情况成为可能。
使用基于人抗人CD154单克隆抗体的免疫抑制方案，在狒狒（n = 8）中进行了GalT-KO猪的异位心脏移植。
在8例中的6例中，移植物存活时间延长至约2至6个月。所有移植物均发生血栓性微血管病（TM）。特别总结了1例移植物功能维持179天的狒狒的临床病程。该狒狒从第4天起除肝素外还接受阿司匹林（隔日40mg），这可能是TM发病和进展延迟以及移植物存活时间延长的一个因素。抗CD154单克隆抗体、霉酚酸酯和甲泼尼龙的维持治疗与CD3CD4和CD3CD8细胞数量持续偏低有关。尽管这些细胞持续耗竭，但未发生感染性并发症。
TM是否与移植物上天然预先形成的或T细胞诱导的抗体沉积水平极低从而诱导内皮细胞活化和损伤有关，或者与猪和狒狒凝血机制中的分子不相容性有关，抑或与两者都有关，仍有待确定。然而，此前未见报道的猪器官在狒狒体内功能维持近6个月，这为异种移植障碍最终能够被克服带来了希望。
