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猪器官异种移植在非人类灵长类动物中的复兴景观。

The resurgent landscape of xenotransplantation of pig organs in nonhuman primates.

机构信息

Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.

Institute of Nutrition and Food Safety, Shaanxi Provincial Center for Disease Control and Prevention, Xi'an, 710054, China.

出版信息

Sci China Life Sci. 2021 May;64(5):697-708. doi: 10.1007/s11427-019-1806-2. Epub 2020 Sep 21.

Abstract

Organ shortage is a major bottleneck in allotransplantation and causes many wait-listed patients to die or become too sick for transplantation. Genetically engineered pigs have been discussed as a potential alternative to allogeneic donor organs. Although xenotransplantation of pig-derived organs in nonhuman primates (NHPs) has shown sequential advances in recent years, there are still underlying problems that need to be completely addressed before clinical applications, including (i) acute humoral xenograft rejection; (ii) acute cellular rejection; (iii) dysregulation of coagulation and inflammation; (iv) physiological incompatibility; and (v) cross-species infection. Moreover, various genetic modifications to the pig donor need to be fully characterized, with the aim of identifying the ideal transgene combination for upcoming clinical trials. In addition, suitable pretransplant screening methods need to be confirmed for optimal donor-recipient matching, ensuring a good outcome from xenotransplantation. Herein, we summarize the understanding of organ xenotransplantation in pigs-to-NHPs and highlight the current status and recent progress in extending the survival time of pig xenografts and recipients. We also discuss practical strategies for overcoming the obstacles to xenotransplantation mentioned above to further advance transplantation of pig organs in the clinic.

摘要

器官短缺是同种异体移植的主要瓶颈,导致许多等待移植的患者死亡或病情太重而无法进行移植。基因工程猪已被讨论作为异体供体器官的潜在替代品。尽管近年来在非人类灵长类动物(NHPs)中进行的猪源性器官异种移植取得了一系列进展,但在临床应用之前仍存在需要彻底解决的潜在问题,包括(i)急性体液异种移植排斥反应;(ii)急性细胞排斥反应;(iii)凝血和炎症失调;(iv)生理不相容性;和(v)跨物种感染。此外,需要充分表征猪供体的各种遗传修饰,以确定即将进行的临床试验的理想转基因组合。此外,需要确认合适的移植前筛选方法,以实现最佳的供体-受者匹配,确保异种移植取得良好的效果。本文总结了对猪到 NHPs 的器官异种移植的理解,并强调了延长猪异种移植物和受者存活时间的当前现状和最新进展。我们还讨论了克服异种移植上述障碍的实用策略,以进一步推进临床猪器官移植。

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