Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date.
Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date.
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DOI：
10.1111/xen.12174
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发表时间：
2015-07
影响因子：
3.9
通讯作者：
Cooper DK
中科院分区：
文献类型：
--
作者：
Iwase H;Liu H;Wijkstrom M;Zhou H;Singh J;Hara H;Ezzelarab M;Long C;Klein E;Wagner R;Phelps C;Ayares D;Shapiro R;Humar A;Cooper DK
迄今为止，接受维持生命的肾移植的非人类灵长类动物的最长存活时间为90天，尽管移植肾存活30天的情况并不常见。一只狒狒接受了α1，3-半乳糖基转移酶基因的肾脏移植--转基因猪获得了两种人类补体和三种人类凝血调节蛋白(尽管只有一种在肾脏中表达)。免疫抑制治疗采用ATG+抗CD20mAb诱导治疗和抗CD40mAb+雷帕霉素+糖皮质激素维持治疗。给予抗肿瘤坏死因子-α和抗IL-6R治疗。狒狒存活136天，血肌酐基本稳定(0.6-1.6 mg/dL)，直到绝症。未观察到消耗性凝血障碍(例如，血小板减少、纤维蛋白原降低)或蛋白丢失肾病的特征。没有证据表明有抗猪抗体反应。死亡原因为感染性休克(Myroids spp.)。第103天的活检组织学正常，但到第136天，肾脏出现肾小球增大、血栓和系膜扩张的特征。(I)来自特定基因工程猪的移植物，(Ii)有效的免疫抑制方案，以及(Iii)抗炎剂的组合，可防止免疫损伤和蛋白丢失肾病，以及延迟性凝血功能障碍。这一结果鼓励我们，临床异种肾移植可能成为现实。
The longest survival of a nonhuman primate with a life-supporting kidney graft to date has been 90 days, though graft survival >30 days has been unusual. A baboon received a kidney graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for two human complement- and three human coagulation- regulatory proteins (though only one was expressed in the kidney). Immunosuppressive therapy was with ATG+anti-CD20mAb (induction) and anti-CD40mAb+rapamycin+corticosteroids (maintenance). Anti-TNF-α and anti-IL-6R were administered. The baboon survived 136 days with a generally stable serum creatinine (0.6–1.6mg/dL) until terminally. No features of a consumptive coagulopathy (e.g., thrombocytopenia, decreased fibrinogen) or of a protein-losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response. Death was from septic shock (Myroides spp). Histology of a biopsy on day 103 was normal, but by day 136 the kidney showed features of glomerular enlargement, thrombi, and mesangial expansion. The combination of (i) a graft from a specific genetically-engineered pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory agents prevented immune injury and a protein-losing nephropathy, and delayed coagulation dysfunction. This outcome encourages us that clinical renal xenotransplantation may become a reality.