Department of Pharmacy, Women and Children's Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, China.
Department of Clinical Pharmacy, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Sichuan, China.
Front Immunol. 2022 Dec 6;13:1031185. doi: 10.3389/fimmu.2022.1031185. eCollection 2022.
Xenotransplantation has the potential to solve the shortfall of human organ donors. Genetically modified pigs have been considered as potential animal donors for human xenotransplantation and have been widely used in preclinical research. The genetic modifications aim to prevent the major species-specific barriers, which include humoral and cellular immune responses, and physiological incompatibilities such as complement and coagulation dysfunctions. Genetically modified pigs can be created by deleting several pig genes related to the synthesis of various pig specific antigens or by inserting human complement- and coagulation-regulatory transgenes. Finally, in order to reduce the risk of infection, genes related to porcine endogenous retroviruses can be knocked down. In this review, we focus on genetically modified pigs and comprehensively summarize the immunological mechanism of xenograft rejection and recent progress in preclinical and clinical studies. Overall, both genetically engineered pig-based xenografts and technological breakthroughs in the biomedical field provide a promising foundation for pig-to-human xenotransplantation in the future.
异种移植有可能解决人类器官捐献者短缺的问题。经过基因改造的猪被认为是人类异种移植的潜在动物供体，并已广泛应用于临床前研究。基因改造旨在防止主要的种间特异性障碍，包括体液和细胞免疫反应，以及补体和凝血功能障碍等生理不相容性。通过删除与各种猪特异性抗原合成相关的几个猪基因，或插入人类补体和凝血调节转基因，可以创建经过基因改造的猪。最后，为了降低感染风险，可以敲除与猪内源性逆转录病毒相关的基因。在这篇综述中，我们重点介绍了经过基因改造的猪，并全面总结了异种移植物排斥的免疫学机制以及临床前和临床研究的最新进展。总的来说，基于基因工程猪的异种移植物和生物医学领域的技术突破为未来的猪到人的异种移植提供了有希望的基础。
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