For more than a century, transplantation of tissues and organs from animals into man, xenotransplantation, has been viewed as a potential way to treat disease. Ironically, interest in xenotransplantation was fueled especially by successful application of allotransplantation, that is, transplantation of human tissue and organs, as a treatment for a variety of diseases, especially organ failure because scarcity of human tissues limited allotransplantation to a fraction of those who could benefit. In principle, use of animals such as pigs as a source of transplants would allow transplantation to exert a vastly greater impact than allotransplantation on medicine and public health. However, biological barriers to xenotransplantation, including immunity of the recipient, incompatibility of biological systems, and transmission of novel infectious agents, are believed to exceed the barriers to allotransplantation and presently to hinder clinical applications. One way potentially to address the barriers to xenotransplantation is by genetic engineering animal sources. The last 2 decades have brought progressive advances in approaches that can be applied to genetic modification of large animals. Application of these approaches to genetic engineering of pigs has contributed to dramatic improvement in the outcome of experimental xenografts in nonhuman primates and have encouraged the development of a new type of xenograft, a reverse xenograft, in which human stem cells are introduced into pigs under conditions that support differentiation and expansion into functional tissues and potentially organs. These advances make it appropriate to consider the potential limitation of genetic engineering and of current models for advancing the clinical applications of xenotransplantation and reverse xenotransplantation.

中文翻译：

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异种移植：从模型到应用的不确定路径。

一个多世纪以来，异种移植已被认为是从动物到人的组织器官移植到人类的一种潜在的治疗疾病的方法。具有讽刺意味的是，异种移植的兴趣尤其是通过成功应用同种异体移植（即人体组织和器官的移植）作为多种疾病（尤其是器官衰竭）的治疗而引起，因为人体组织的稀缺将同种异体移植限制在那些效益。原则上，使用诸如猪之类的动物作为移植来源将使移植比同种异体移植对医学和公共卫生产生更大的影响。但是，异种移植的生物学障碍包括受体的免疫力，生物系统的不相容性以及新型传染因子的传播，据信，其已经超过了同种异体移植的障碍，目前阻碍了临床应用。解决异种移植障碍的一种可能方法是通过基因工程动物来源。在过去的20年中，可应用于大型动物基因改造的方法取得了进步。这些方法在猪的基因工程中的应用极大地改善了非人灵长类动物实验异种移植的结果，并鼓励了新型异种移植（反向异种移植）的发展，在这种条件下，人类干细胞可以在猪中引入支持分化并扩展到功能组织和潜在器官。