Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
Xenotransplantation. 2019 Jul;26(4):e12504. doi: 10.1111/xen.12504. Epub 2019 Mar 2.
The humoral barrier has been the limiting factor in moving xenotransplantation towards the clinic. Improvements in somatic cell nuclear transfer and genome editing, particularly CRISPR-Cas9, have made it possible to create pigs with multiple glycan xenoantigen deletions for the purposes of reducing xenoreactive antibody binding to the xenografted organ. Recent studies have also considered the aetiology and existence of antibodies directed at the swine leucocyte antigen (SLA) complex, and potential genetic engineering strategies to avoid these antibodies. Evaluation of xenoreactive antibody binding is very important for the advancement of xenotransplantation, because if patients do not have any detectable xenoreactive antibody, then it is reasonable to expect that cellular rejection and not antibody-mediated rejection (AMR) will be the next hurdle to clinical application.
体液屏障一直是将异种移植推向临床应用的限制因素。体细胞核移植和基因组编辑技术的改进,特别是 CRISPR-Cas9 技术,使得创建具有多种聚糖异种抗原缺失的猪成为可能,目的是减少异种反应性抗体与异种移植器官的结合。最近的研究还考虑了针对猪白细胞抗原 (SLA) 复合物的抗体的病因和存在,以及潜在的基因工程策略来避免这些抗体。异种反应性抗体结合的评估对于异种移植的发展非常重要,因为如果患者没有检测到任何异种反应性抗体,那么可以合理地预期细胞排斥而不是抗体介导的排斥 (AMR) 将是临床应用的下一个障碍。