Immunological, physiological, and biosafety challenges in xenotransplantation
10.3760/cma.j.cn113855-20241210-00765
- VernacularTitle:异种移植免疫学、生理学与生物安全挑战
- Author:
Xuan ZHANG
1
;
Kefeng DOU
1
Author Information
1. 空军军医大学第一附属医院肝胆外科，西安 710032
- Publication Type:Journal Article
- Keywords:
Transplantation immunology;
Physiology;
Xenotransplantation;
Biosafety;
Gene editing
- From:
Chinese Journal of General Surgery
2025;40(1):18-22
- CountryChina
- Language:Chinese
-
Abstract:
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.
