Immunology Research Centre, St Vincent's Hospital Melbourne, Victoria, Australia.
Department of Medicine, University of Melbourne, Victoria, Australia.
Am J Transplant. 2017 Oct;17(10):2531-2536. doi: 10.1111/ajt.14311. Epub 2017 May 8.
There has been an upsurge of interest in xenotransplantation in recent years. This resurgence can attributed to a combination of factors. First, there has been a dramatic improvement in efficacy in several preclinical models, with maximum xenograft survival times increasing to 950 days for islets, 945 days for hearts, and 310 days for kidneys. Second, the rapid development of genome editing technology (particularly the advent of clustered regularly interspaced short palindromic repeats/Cas9) has revolutionized the capacity to generate new donor pigs with multiple protective genetic modifications; what once took many years to achieve can now be performed in months, with much greater precision and scope. Third, the specter of porcine endogenous retrovirus (PERV) has receded significantly. There has been no evidence of PERV transmission in clinical trials and preclinical models, and improved screening methods and new options for the treatment or even elimination of PERV are now available. Balancing these positive developments are several remaining challenges, notably the heavy and often clinically inapplicable immunosuppression required to prevent xenograft rejection. Nonetheless, the potential for xenotransplantation as a solution to the shortage of human organs and tissues for transplantation continues to grow.
近年来，异种移植的研究兴趣激增。这种复苏可以归因于多种因素的结合。首先，在几种临床前模型中，疗效有了显著提高，最大异种移植物存活时间达到胰岛 950 天、心脏 945 天和肾脏 310 天。其次，基因组编辑技术（特别是簇状规律间隔短回文重复序列/Cas9 的出现）的快速发展彻底改变了生成具有多种保护遗传修饰的新型供体猪的能力；曾经需要多年才能实现的目标，现在可以在几个月内完成，而且精度和范围都大大提高。第三，猪内源性逆转录病毒（PERV）的威胁已经大大降低。在临床试验和临床前模型中均未发现 PERV 传播的证据，现在有了改进的筛选方法和新的治疗方法，甚至可以消除 PERV。平衡这些积极发展的是几个仍然存在的挑战，特别是预防异种移植物排斥所需的沉重且通常临床上不适用的免疫抑制。尽管如此，异种移植作为解决人类器官和组织移植短缺问题的一种解决方案的潜力仍在不断增长。
