Preclinical Studies in Xenotransplantation

异种移植的临床前研究

• 批准号: nhmrc : 394900
• 负责人: A/Pr Mark Nottle
• 金额: $ 79.75万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/preclinical-studies-xenotransplantation/96578
• 关键词: Preclinical; Studies; Xenotransplantation

Many people with organ failure such as heart or kidney disease need a transplant to survive. In the case of kidney failure patients can be kept alive by the artificial kidney however this sort of mechanical traeatment is much less satisfactory than a transplant. Unfortunately most patients who would benefit from a transplant are unable to receive one beacuse of the shortage of living or cadaver donors. A possible solution to this shortage of organs for transplantation is to use animal organs. Pigs are the most suitable animal donor. However, a pig-to-human organ is rejected immediatly because of the distance between the species. Over the last 10 years, we and others have been trying to understand which genetic differences are important. It is now clear that there are several important differences. One of these is a Blood Group like molecule in the pig that humans react with immediatly on transplantation. This is called the Gal molecule. We and others have been successful in removing the pig gene that makes this molecule. In addition we have added several human genes to pigs to prevent the early vigorous rejection which usually occurs. Organs from these genetically modified pigs have been tested by transplantation into baboons and monkeys. The transplants which used to be rejected within minutes, now survive for months. However, they organs are still rejected by a process which causes clotting in the transplanted organs. We now understand the mechanism andare making genetically modified pigs with human genes which regulate clotting of human blood. This project will test organs from these pigs by transplantation into baboons. We will also make a special strain of pigs in which all these genetic modifications are assembled. This involves the removal of one pig gene and the addition of 4 or 5 human genes. We think it is highly likely that this combination of genetic modifications will make this strain of pigs much more suitable as organ donors.

许多患有心脏病或肾病等器官衰竭的人需要移植才能生存。在肾衰竭的情况下，病人可以通过人工肾维持生命，然而这种机械治疗远不如移植令人满意。不幸的是，由于缺乏活体或尸体供体，大多数能从移植中受益的患者无法接受移植。解决器官移植短缺的一个可能的办法是使用动物器官。猪是最合适的动物供体。然而，由于物种之间的距离，猪到人类的器官被立即拒绝。在过去的10年里，我们和其他人一直在试图了解哪些遗传差异是重要的。现在很清楚，有几个重要的区别。其中之一是猪体内的一种血型样分子，人类在移植时会立即发生反应。这就是所谓的Gal分子。我们和其他人已经成功地去除了制造这种分子的猪基因。此外，我们还在猪身上添加了几种人类基因，以防止通常发生的早期强烈排斥反应。这些转基因猪的器官已经通过移植到狒狒和猴子身上进行了测试。过去几分钟内就被排斥的移植，现在可以存活数月。然而，它们的器官仍然会被一个过程所排斥，这个过程会导致移植器官中的凝血。我们现在已经了解了这一机制，并正在制造带有人类基因的转基因猪，这些基因可以调节人类血液的凝固。该项目将通过将这些猪的器官移植到狒狒身上来测试。我们还将制造一种特殊的猪种，在这种猪种中，所有这些基因修饰都被组装起来。这涉及去除一个猪基因并添加4或5个人类基因。我们认为，这种基因改造的组合很可能会使这种猪更适合作为器官捐赠者。