Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
J Transl Med. 2024 Apr 2;22(1):324. doi: 10.1186/s12967-024-05136-4.
The shortage of organs for transplantation emphasizes the urgent need for alternative solutions. Xenotransplantation has emerged as a promising option due to the greater availability of donor organs. However, significant hurdles such as hyperacute rejection and organ ischemia-reperfusion injury pose major challenges, largely orchestrated by the complement system, and activated immune responses. The complement system, a pivotal component of innate immunity, acts as a natural barrier for xenotransplantation. To address the challenges of immune rejection, gene-edited pigs have become a focal point, aiming to shield donor organs from human immune responses and enhance the overall success of xenotransplantation. This comprehensive review aims to illuminate strategies for regulating complement networks to optimize the efficacy of gene-edited pig xenotransplantation. We begin by exploring the impact of the complement system on the effectiveness of xenotransplantation. Subsequently, we delve into the evaluation of key complement regulators specific to gene-edited pigs. To further understand the status of xenotransplantation, we discuss preclinical studies that utilize gene-edited pigs as a viable source of organs. These investigations provide valuable insights into the feasibility and potential success of xenotransplantation, offering a bridge between scientific advancements and clinical application.
器官移植的短缺凸显了寻找替代解决方案的迫切需求。由于供体器官的可用性增加,异种移植已成为一种很有前途的选择。然而,由于补体系统和激活的免疫反应等因素,超急性排斥反应和器官缺血再灌注损伤等重大障碍仍然存在。补体系统是先天免疫系统的关键组成部分,是异种移植的天然屏障。为了应对免疫排斥的挑战,基因编辑猪已成为焦点,旨在保护供体器官免受人体免疫反应的影响,并提高异种移植的整体成功率。本综述旨在阐明调节补体网络的策略,以优化基因编辑猪异种移植的效果。我们首先探讨了补体系统对异种移植效果的影响。随后,我们深入研究了针对基因编辑猪的关键补体调节剂的评估。为了进一步了解异种移植的现状,我们讨论了利用基因编辑猪作为可行器官来源的临床前研究。这些研究为异种移植的可行性和潜在成功提供了有价值的见解,在科学进步和临床应用之间架起了桥梁。