Xenotransplantation Research Center, Seoul National University, College of Medicine, Seoul, South Korea.
Department of Microbiology and Immunology, Seoul National University, College of Medicine, Seoul, South Korea.
Curr Diab Rep. 2021 Jan 12;21(1):3. doi: 10.1007/s11892-020-01368-y.
Porcine islet xenotransplantation is a promising alternative to overcome the shortage of organ donors. For the successful application of islet xenotransplantation, robust immune/inflammatory responses against porcine islets should be thoroughly controlled. Over the last few decades, there have been numerous attempts to surmount xenogeneic immune barriers. In this review, we summarize the current progress in immunomodulatory therapy for the clinical application of porcine islet xenotransplantation.
Long-term graft survival of porcine islets was achieved by using anti-CD154 Ab-based regimens in a preclinical non-human primate (NHP) model. However, owing to a serious complication of thromboembolism in clinical trials, the development of an anti-CD154 Ab-sparing immunosuppressant procedure is required. The efficacy of new immunosuppressive practices that employ anti-CD40 Abs or other immunosuppressive reagents has been tested in a NHP model to realize their utility in porcine islet xenotransplantation. The recent progress in the development of immunomodulatory approaches, including the immunosuppressive regimen, which enables long-term graft survival in a pig-to-non-human primate islet xenotransplantation model, with their potential clinical applicability was reviewed.
猪胰岛异种移植是克服器官供体短缺的一种很有前途的方法。为了成功应用胰岛异种移植,需要彻底控制针对猪胰岛的强大免疫/炎症反应。在过去的几十年中,人们已经进行了多次尝试来克服异种免疫屏障。在这篇综述中,我们总结了用于临床应用的猪胰岛异种移植的免疫调节治疗的最新进展。
在非人类灵长类动物(NHP)模型中,使用基于抗 CD154Ab 的方案可实现猪胰岛的长期移植物存活。然而,由于临床试验中出现严重的血栓栓塞并发症,因此需要开发一种无需抗 CD154Ab 的免疫抑制剂方案。在 NHP 模型中已经测试了新型免疫抑制方法的疗效,这些方法使用抗 CD40Ab 或其他免疫抑制试剂,以实现其在猪胰岛异种移植中的应用。最近在免疫调节方法的开发方面取得了进展,包括能够在猪到非人类灵长类动物胰岛异种移植模型中实现长期移植物存活的免疫抑制方案,及其潜在的临床适用性进行了综述。