基因修饰猪-非人灵长类动物异种肾移植面临的问题及挑战

Problems and challenges of genetically modified pig to non-human primate kidney xenotransplantation

异种肾移植是解决供肾短缺的潜在方法之一。随着基因修饰技术的进步和免疫抑制药的更新发展,目前基因修饰猪-非人灵长类动物(NHP)异种肾移植临床前研究取得了重大的进步,受体最长存活时间超过500 d,但存活时间超过1年的例数很少,大多数受体在移植术后1~2个月内死亡。因此,仍有一些问题需要明确并解决。本文通过对基因修饰猪-NHP异种肾移植中排斥反应、难治性凝血功能紊乱、持续存在的炎症反应、免疫抑制药的选择、临床受者的选择、交叉感染风险等问题进行综述,总结基因修饰猪-NHP异种肾移植目前所面临的问题及可能解决的方法,为促进临床异种肾移植提供参考。

Xenotransplantation is one of the potential approaches to mitigate the shortage of donor kidneys.With the progress of gene modification techniques and the development of immunosuppressant,significant progress has been made in the preclinical research of genetically modified pig to non-human primate(NHP)xenotransplantation.The longest survival time of recipients exceeds 500 d.However,the number of recipients surviving for over 1 year is extremely low,and most recipients die within postoperative 1-2 months.Therefore,several problems remain to be clarified and resolved.In this article,rejection,refractory coagulation dysfunction,persistent inflammation,the selection of immunosuppressant,the selection of clinical recipients and the risk of cross-infection in genetically modified pig to NHP xenotransplantation were reviewed,and current problems and potential solutions of genetically modified pig to NHP xenotransplantation were summarized,aiming to provide reference for promoting xenotransplantation in clinical settings.