Department of Pathology, University of New Mexico, and Cancer Research and Treatment Center, Albuquerque, NM, USA.
Cell Transplant. 2013;22(10):1943-54. doi: 10.3727/096368912X657963. Epub 2012 Oct 12.
Organ transplantation is a life-saving procedure and the preferred method of treatment for a growing number of disease states. The advent of new immunosuppressants and improved care has led to great advances in both patient and graft survival. However, acute T-cell-mediated graft rejection occurs in a significant quantity of recipients and remains a life-threatening condition. Acute rejection is associated with decrease in long-term graft survival, demonstrating a need to carefully monitor transplant patients. Current diagnostic criteria for transplant rejection rely on invasive tissue biopsies or relatively nonspecific clinical features. A noninvasive way is needed to detect, localize, and monitor transplant rejection. Capitalizing on advances in targeted contrast agents and magnetic-based detection technology, we developed anti-CD3 antibody-tagged nanoparticles. T cells were found to bind preferentially to antibody-tagged nanoparticles, as identified through light microscopy, transmission electron microscopy, and confocal microscopy. Using mouse skin graft models, we were also able to demonstrate in vivo vascular delivery of T-cell targeted nanoparticles. We conclude that targeting lymphocytes with magnetic nanoparticles is conducive to developing a novel, noninvasive strategy for identifying transplant rejection.
器官移植是一种挽救生命的手术,也是越来越多种疾病状态的首选治疗方法。新型免疫抑制剂和更好的护理手段的出现,使得患者和移植物的存活率都有了显著提高。然而,大量受者仍会发生急性 T 细胞介导的移植物排斥反应,这仍然是一种危及生命的情况。急性排斥反应与长期移植物存活率下降有关,这表明需要仔细监测移植患者。目前,移植排斥反应的诊断标准依赖于有创的组织活检或相对非特异性的临床特征。因此,需要一种非侵入性的方法来检测、定位和监测移植排斥反应。我们利用靶向对比剂和基于磁的检测技术的进步,开发了抗 CD3 抗体标记的纳米颗粒。通过光学显微镜、透射电子显微镜和共聚焦显微镜,发现 T 细胞优先与抗体标记的纳米颗粒结合。利用小鼠皮肤移植模型,我们还能够证明 T 细胞靶向纳米颗粒在体内的血管递呈。我们的结论是,用磁性纳米颗粒靶向淋巴细胞有助于开发一种新颖的、非侵入性的策略来识别移植排斥反应。