Fishman Jay A, Denner Joachim, Scobie Linda
Harvard Medical School, Transplant Infectious Disease and, Compromised Host Program and Transplant Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Laboratory for Virus Safety of Xenotransplantation, Institute of Virology, Free University Berlin, Berlin, Germany.
Xenotransplantation. 2025 Mar-Apr;32(2):e70001. doi: 10.1111/xen.70001.
Clinical xenotransplantation has the potential to address shortages of human organs for patients with end-stage organ failure. Advances in genetic engineering, immunosuppressive regimens, and infectious disease diagnostics have improved prospects for clinical xenotransplantation. Management of the infectious risks posed by clinical xenotransplantation requires biosecure breeding and validated methods for microbiological surveillance of source animals and recipients. Novel infection control protocols may complement biosafety requirements. Infectious risks in xenotransplantation include both known human pathogens common to immunosuppressed organ recipients and from porcine organisms or xenozoonoses for which the clinical manifestations are less well defined and for which microbial assays and therapies are more limited. Some pig-specific organisms do not infect human cells but have systemic manifestations when active within the xenograft. The human risk posed by porcine endogenous retroviruses (PERV) is uncertain. There are no documented transmissions of PERV in humans and swine are available with inactivated genomic PERV loci. Metagenomic sequencing will complement more traditional diagnostic tools in the detection of any unknown pathogens in xenotransplantation recipients. Such data are required for the development of protocols for donor and recipient microbiological surveillance, infection control, and antimicrobial therapies that will enhance the safety of clinical xenotransplantation.
临床异种移植有潜力解决终末期器官衰竭患者人体器官短缺的问题。基因工程、免疫抑制方案及传染病诊断方面的进展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生物安全养殖以及针对供体动物和受体的微生物监测的验证方法。新型感染控制方案可补充生物安全要求。异种移植中的感染风险包括免疫抑制器官受体常见的已知人类病原体，以及来自猪源生物体或人畜共患病原体，后者的临床表现较不明确，微生物检测和治疗方法也较为有限。一些猪特有的生物体不会感染人类细胞，但在异种移植物中活跃时会出现全身表现。猪内源性逆转录病毒（PERV）对人类构成的风险尚不确定。尚无PERV在人类中传播的记录，且可获得基因组PERV位点失活的猪。宏基因组测序将补充更传统的诊断工具，用于检测异种移植受体中的任何未知病原体。这些数据对于制定供体和受体微生物监测、感染控制及抗菌治疗方案至关重要，这些方案将提高临床异种移植的安全性。
