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The resurgent landscape of xenotransplantation of pig organs in nonhuman primates

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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.

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Acknowledgements

This work was supported by the National Basic Research Program of China (2015CB554100), the National Key Research and Development Program of China (2017YFC1103703), the National Natural Science Foundation of China (81870446, 81671838, 81670593, 81900571), Natural Science Foundation of Shaanxi Province (2016JM8026, 2020JQ-451), and Academic Assistant Program of Xijing Hospital (XJZT18MJ29, XJZT18MJ27).

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

    Xuan Zhang, Quancheng Wang, Xiao Li, Wei Peng, Zhaoxu Yang, Zhibin Lin, Long Yang, Rui Ding, Kaishan Tao & Kefeng Dou

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

    Jingjun Zhao

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Zhang, X., Wang, Q., Zhao, J. et al. The resurgent landscape of xenotransplantation of pig organs in nonhuman primates. Sci. China Life Sci. 64, 697–708 (2021). https://doi.org/10.1007/s11427-019-1806-2

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