Cooper D K
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Front Biosci. 1996 Sep 1;1:d248-65. doi: 10.2741/a130.
Organ transplantation is limited by the number of cadaveric human donor organs that become available. Xenotransplantation--the transplantation of organs and tissues between animal species--would supply an unlimited number of organs and offer many other advantages. The pig has been identified as the most suitable donor animal. Pig organs, when transplanted into humans or nonhuman primates, are, however, rejected hyperacutely within minutes by antibody-mediated complement activation. Human anti-pig antibodies have been identified as being directed against Gal alpha1-3galactose epitopes on pig vascular endothelium. Major efforts are being made to overcome this hyperacute rejection. Methods being investigated include (i) depletion or inhibition of recipient antibodies or complement, (ii) development of transgenic pigs that do not express the alphaGal epitope and/or express a human complement inhibiting protein (e.g. DAF), and (iii) development of immunological tolerance to pig organs in the recipient. If complement activation is prevented, e.g. by inhibition of complement activation by cobra venom factor, soluble complement receptor 1 or by the use of hDAF transgenic pig organs, then "delayed xenograft rejection" occurs and is again believed to be largely antibody-dependent. Experimental pig-to-primate organ xenotransplantation is now, however, resulting in transplant function for days and weeks rather than minutes, and there is therefore optimism that we are on the threshold of a new era in the field of the transplantation of vital organs.
器官移植受到可获得的人类尸体供体器官数量的限制。异种移植——不同动物物种之间的器官和组织移植——将提供数量无限的器官，并具有许多其他优势。猪已被确定为最合适的供体动物。然而，猪器官移植到人类或非人类灵长类动物体内时，会在几分钟内通过抗体介导的补体激活而被超急性排斥。已确定人类抗猪抗体是针对猪血管内皮上的Galα1-3半乳糖表位。目前正在做出重大努力来克服这种超急性排斥。正在研究的方法包括：（i）清除或抑制受体抗体或补体；（ii）培育不表达αGal表位和/或表达人类补体抑制蛋白（如衰变加速因子）的转基因猪；（iii）使受体对猪器官产生免疫耐受。如果补体激活被阻止，例如通过眼镜蛇毒因子、可溶性补体受体1抑制补体激活或使用人衰变加速因子转基因猪器官，那么就会发生“延迟性异种移植排斥”，并且再次被认为主要依赖抗体。然而，目前猪到灵长类动物的实验性器官异种移植已经能使移植器官维持数天甚至数周的功能，而不是几分钟，因此人们乐观地认为，我们正处于重要器官移植领域新时代的开端。
