Petersen Bjoern, Carnwath Joseph W, Niemann Heiner
Institute of Farm Animal Genetics (FLI), Department of Biotechnology, Hoeltystrasse 10, 31535 Neustadt, Germany.
Comp Immunol Microbiol Infect Dis. 2009 Mar;32(2):91-105. doi: 10.1016/j.cimid.2007.11.014. Epub 2008 Feb 15.
The shortage of donated human organs for transplantation continues to be a life threatening problem for patients suffering from complete organ failure. Although this gap is increasing due to the demographic changes in aging Western populations, it is generally accepted that international trading in human organ is not an ethical solution. Alternatives to the use of human organs for transplantation must be developed and these alternatives include stem cell therapy, artificial organs and organs from other species, i.e. xenografts. For practical reasons but most importantly because of its physiological similarity with humans, the pig is generally accepted as the species of choice for xenotransplantation. Nevertheless, before porcine organs can be used in human xenotransplantation, it is necessary to make a series of precise genetic modifications to the porcine genome, including the addition of genes for factors which suppress the rejection of transplanted porcine tissues and the inactivation or removal of undesirable genes which can only be accomplished at this time by targeted recombination and somatic nuclear transfer. This review will give an insight into the advances in transgenic manipulation and cloning in pigs--in the context of porcine-to-human xenotransplantation.
用于移植的人体捐赠器官短缺,对于患有完全器官衰竭的患者来说仍然是一个危及生命的问题。尽管由于西方人口老龄化的人口结构变化,这一缺口在不断扩大,但人们普遍认为,人体器官的国际贸易并非道德的解决方案。必须开发用于移植的人体器官替代方案,这些替代方案包括干细胞疗法、人造器官和来自其他物种的器官,即异种移植。出于实际原因,但最重要的是由于猪与人类在生理上的相似性,猪通常被认为是异种移植的首选物种。然而,在猪器官可用于人类异种移植之前,有必要对猪基因组进行一系列精确的基因改造,包括添加抑制移植猪组织排斥反应的因子基因,以及使不良基因失活或去除,目前这只能通过靶向重组和体细胞核移植来实现。本综述将深入探讨猪的转基因操作和克隆技术在猪到人的异种移植背景下的进展。