异种器官移植的进展及展望

Progress and Perspective for Xenotransplantation

在全球范围内,因终末期器官衰竭而需要器官移植的患者人数不断增加,但从已故或活体捐赠者获得的器官数量非常有限。因此,利用猪器官/组织进行异种移植是解决器官供给短缺的最终办法之一。尽管异种器官移植的研究取得了很大进展,然而,要真正走向临床仍然存在许多障碍,特别是免疫排斥问题。随着该领域研究的不断深入,特别是各种基因编辑技术的发展,实现对猪产生超急性排斥的基因敲除及猪的多种基因进行人源化改造,再在非人类灵长类动物移植模型中进行安全性及功能性评估,移植器官的存活率显著提高。利用CRISPR/Cas9技术将猪内源性逆转录病毒(PERV)从猪基因组中去除,避免了异种器官移植后内源性病原体感染宿主的潜在风险,具有里程碑意义。本文对异种移植研究需要跨越的障碍、进展、安全、监管和现状等进行了综述。

Worldwide,the number of patients needing organ transplants for end-stage organ failure is growing,however￡? the number of organs available from donation after cardiac death/donation after brain death(DCD/DBD) or living donors is very limited.Therefore,the use of pig organs/tissues for xenotransplantation is one of the final solutions for the shortage of organs.Although tremendous progress has been made in xenotransplantation research,there are still some huge hurdlers,especially immune rejection,in the clinical application of xenotransplantation.With the continuous progress of the field,especially the development of various gene editing technologies,knocking out specific porcine genes which cause hyperacute rejection and humanizing multiple genes in pigs become possible,the survival of transplanted organs in the models of non-human primates has been significantly improved.Moreover,the application of CRISPR/Cas9 technology to remove porcine endogenous retroviruses(PERV) from the pig genome eliminates the potential risk of endogenous pathogens infecting the host after xenotransplantation,which is of landmark significance.This work reviews the barriers,progress,safety,oversight and current status of xenotransplantation.