异种移植免疫学、生理学与生物安全挑战  

Immunological,physiological,and biosafety challenges in xenotransplantation

作　　者：张玄 窦科峰 Zhang Xuan;Dou Kefeng(Department of Hepatobiliary Surgery,First Affiliated Hospital of Air Force Medical University,Xi'an 710032,China)

机构地区：[1]空军军医大学第一附属医院肝胆外科,西安710032

出　　处：《中华普通外科杂志》2025年第1期18-22,共5页Chinese Journal of General Surgery

基　　金：国家自然科学基金(82371793、82070671);国家重点研发计划项目(2024YFC3406802)。

摘　　要：以猪为供体的异种移植被认为是解决同种器官短缺问题最具潜力的途径之一,近年来获得了飞速发展。但是,现阶段异种移植走向临床仍面临着免疫排斥、生理兼容与生物安全等方面的挑战。其中,体液性排斥是影响异种移植物长期存活的主要障碍,而人类受者可能对三基因敲除供体猪仍有预存抗体。尽管如此,早期抗体介导的体液性排斥仍然是可以预防的。同时,细胞性排斥和炎症反应亦与移植物的长期存活密切相关,供体猪转入人源化分子,联合受体使用抗炎药物可以帮助改善异种移植物存活。此外,生理学挑战主要体现在凝血级联反应的不兼容,以及猪蛋白与人蛋白在结构和功能上的差异。生物安全方面,培育无指定病原体供体猪和开发高灵敏度的猪源微生物检测方法是降低移植排斥和种间感染的关键。现阶段,仍需进一步攻关基因编辑策略、免疫抑制方案和感染监测手段,以改善移植物和受体的长期存活。Xenotransplantation using pigs as donors is considered one of the most promising approaches to address the shortage of allogeneic organs and has been seen rapid development in recent years.However,the clinical application of xenotransplantation still faces challenges in immune rejection,physiological compatibility,and biosafety.Among these,humoral rejection is a major barrier affecting the long-term survival of xenografts,and human recipients may have pre-existing antibodies against triple gene knockout(TKO)donor pigs.Nevertheless,early antibody-mediated humoral rejection can still be prevented.Additionally,cellular rejection and inflammatory responses are closely related to the long-term survival of grafts,and the introduction of humanized molecules in donor pigs,combined with the use of anti-inflammatory drugs by recipients,can help improve the survival of xenografts.Moreover,physiological challenges are mainly reflected in the incompatibility of the coagulation cascade and the structural and functional differences between pig proteins and human proteins.In terms of biosafety,breeding donor pigs free of designed pathogens and developing highly sensitive detection methods for pig-derived microorganisms are key to reduce transplant rejection and interspecies infections.At present,further research is needed in gene editing strategies,immunosuppressive regimens,and infection monitoring methods to improve the long-term survival of grafts and recipients.

关 键 词：移植免疫学 生理学 异种移植 生物安全 基因编辑 

分 类 号：R392.4[医药卫生—免疫学]