Stewart Adam G, Fishman Jay A
Transplant Infectious Disease and Compromised Host Program, MGH Transplant Center, Harvard Medical School, Boston, Massachusetts, USA.
Clin Microbiol Rev. 2025 Mar 13;38(1):e0015023. doi: 10.1128/cmr.00150-23. Epub 2025 Jan 31.
SUMMARYXenotransplantation, the transplantation of living organs, tissues, or cells between species, carries the potential to address the global shortage of human organs for patients with end-stage organ failure. Recent advances in genetic engineering have improved prospects for clinical xenotransplantation by reducing immune and inflammatory responses to grafts, controlling coagulation on endothelial surfaces, and modifying viral risks, including the porcine endogenous retrovirus (PERV). Management of infectious risks posed by clinical xenotransplantation requires meticulous attention to the biosecure breeding and microbiological surveillance of source animals and recipients and consideration of novel infection control requirements. Infectious risks in xenotransplantation stem from both known human pathogens in immunosuppressed transplant recipients and from porcine organisms for which the clinical manifestations, microbial assays, and therapies are generally limited. Both known and unknown zoonoses may be transmitted from pigs to humans. Some pig-specific pathogens do not infect human cells but have systemic manifestations when active within the xenograft, including porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV), which contributes to graft rejection and consumptive coagulopathy. The role of porcine endogenous retrovirus (PERV) in humans remains uncertain despite the absence of documented transmissions and the availability of swine with inactivated genomic PERV. New technologies, such as metagenomic sequencing and multi-omics approaches, will be essential for detection of novel infections and for understanding interactions between the xenograft, the host's immune system, and potential pathogens. These approaches will allow development of infection control protocols, pathogen surveillance requirements, and tailored antimicrobial therapies to enhance the safety and success of clinical xenotransplantation.
摘要
异种移植，即将活体器官、组织或细胞在不同物种间进行移植，有可能解决全球终末期器官衰竭患者人体器官短缺的问题。基因工程的最新进展通过减少对移植物的免疫和炎症反应、控制内皮表面的凝血以及改变包括猪内源性逆转录病毒（PERV）在内的病毒风险，改善了临床异种移植的前景。应对临床异种移植带来的感染风险需要密切关注源动物和受体的生物安全饲养及微生物监测，并考虑新的感染控制要求。异种移植中的感染风险既源于免疫抑制的移植受者体内已知的人类病原体，也源于猪的病原体，而这些病原体的临床表现、微生物检测方法和治疗手段通常都很有限。已知和未知的人畜共患病都可能从猪传播给人类。一些猪特有的病原体不会感染人类细胞，但在异种移植物内活跃时会出现全身表现，包括猪巨细胞病毒/猪玫瑰疹病毒（PCMV/PRV），它会导致移植物排斥和消耗性凝血病。尽管没有记录到猪内源性逆转录病毒（PERV）传播给人类的情况，且存在基因组PERV失活的猪，但PERV在人类中的作用仍不确定。宏基因组测序和多组学方法等新技术对于检测新感染以及了解异种移植物、宿主免疫系统和潜在病原体之间的相互作用至关重要。这些方法将有助于制定感染控制方案、病原体监测要求以及量身定制的抗菌疗法，以提高临床异种移植的安全性和成功率。
