The increasing life expectancy of humans has led to a growing numbers of patients with chronic diseases and end-stage organ failure. Transplantation is an effective approach for the treatment of end-stage organ failure; however, the imbalance between organ supply and the demand for human organs is a bottleneck for clinical transplantation. Therefore, xenotransplantation might be a promising alternative approach to bridge the gap between the supply and demand of organs, tissues, and cells; however, immunological barriers are limiting factors in clinical xenotransplantation. Thanks to advances in gene-editing tools and immunosuppressive therapy as well as the prolonged xenograft survival time in pig-to-non-human primate models, clinical xenotransplantation has become more viable. In this review, we focus on the evolution and current status of xenotransplantation research, including our current understanding of the immunological mechanisms involved in xenograft rejection, genetically modified pigs used for xenotransplantation, and progress that has been made in developing pig-to-pig-to-non-human primate models. Three main types of rejection can occur after xenotransplantation, which we discuss in detail: (1) hyperacute xenograft rejection, (2) acute humoral xenograft rejection, and (3) acute cellular rejection. Furthermore, in studies on immunological rejection, genetically modified pigs have been generated to bridge cross-species molecular incompatibilities; in the last decade, most advances made in the field of xenotransplantation have resulted from the production of genetically engineered pigs; accordingly, we summarize the genetically modified pigs that are currently available for xenotransplantation. Next, we summarize the longest survival time of solid organs in preclinical models in recent years, including heart, liver, kidney, and lung xenotransplantation. Overall, we conclude that recent achievements and the accumulation of experience in xenotransplantation mean that the first-in-human clinical trial could be possible in the near future. Furthermore, we hope that xenotransplantation and various approaches will be able to collectively solve the problem of human organ shortage.

中文翻译：

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异种移植：临床前研究的现状。

人类不断增长的预期寿命导致越来越多的慢性疾病和末期器官衰竭患者。移植是治疗晚期器官衰竭的有效方法。然而，器官供应与人体器官需求之间的不平衡是临床移植的瓶颈。因此，异种移植可能是弥合器官，组织和细胞供求之间差距的有前途的替代方法。然而，免疫屏障是临床异种移植的限制因素。得益于基因编辑工具和免疫抑制疗法的进步，以及在猪到非人类灵长类动物模型中异种移植的延长生存时间，临床异种移植变得更加可行。在这篇评论中 我们专注于异种移植研究的发展和现状，包括我们对异种移植排斥反应涉及的免疫机制，用于异种移植的转基因猪的了解以及在开发猪到猪到非猪的过程中所取得的进展。灵长类动物模型。异种移植后可能发生三种主要类型的排斥，我们将详细讨论：（1）超急性异种移植排斥，（2）急性体液异种排斥和（3）急性细胞排斥。此外，在免疫排斥研究中，已经产生了转基因猪，以弥合跨物种的分子不相容性。在过去的十年中，异种移植领域的大多数进展都来自转基因猪的生产。因此，我们总结了目前可用于异种移植的转基因猪。接下来，我们总结了近年来临床前模型中实体器官的最长生存时间，包括心脏，肝脏，肾脏和肺异种移植。总的来说，我们得出的结论是，异种移植的最新成就和经验的积累意味着在不久的将来可能进行首次人类临床试验。此外，我们希望异种移植和各种方法能够共同解决人体器官短缺的问题。我们得出的结论是，异种移植的最新成就和经验的积累意味着在不久的将来可能进行首次人类临床试验。此外，我们希望异种移植和各种方法能够共同解决人体器官短缺的问题。我们得出的结论是，异种移植的最新成就和经验的积累意味着在不久的将来可能进行首次人类临床试验。此外，我们希望异种移植和各种方法能够共同解决人体器官短缺的问题。