Xu Weicheng, Boer Karin, Hesselink Dennis A, Baan Carla C
Department of Internal Medicine, Sector Nephrology and Transplantation, Erasmus MC Transplant Institute, University Medical Center Rotterdam Erasmus MC, Doctor Molewaterplein 40, Room Nc 508, 3015 GD, Rotterdam, The Netherlands.
BioDrugs. 2025 May;39(3):445-459. doi: 10.1007/s40259-025-00713-5. Epub 2025 Mar 26.
Recent advances in extracellular vesicle (EV) research in organ transplantation have highlighted the crucial role of donor-derived EVs in triggering alloimmune responses, ultimately contributing to transplant rejection. Following transplantation, EVs carrying donor major histocompatibility complex (MHC) molecules activate recipient antigen-presenting cells (APCs), initiating both alloreactive and regulatory T-cell responses. While immunosuppressive drugs are essential for preventing rejection, they may also influence the biogenesis and release of EVs from donor cells. This review examines the impact of maintenance immunosuppressive therapy on EV biogenesis and release post-transplantation. In addition, EV release and uptake may be influenced by specific factors such as the patient's end-stage organ disease and the transplant procedure itself. In-vitro studies using primary human parenchymal and immune cells-integrated with cutting-edge multi-omics techniques, including genomics, proteomics, lipidomics, and single-EV analysis-will offer deeper insights into EV biology and the mechanisms by which immunosuppressive agents regulate EV-initiated immune processes. A detailed understanding of how organ failure, the transplantation procedure and immunosuppressive drugs affect the biology of EVs may uncover new roles for EVs in immune activation and regulation in patients, ultimately leading to improved immunosuppressive strategies and better transplant outcomes.
细胞外囊泡（EV）在器官移植研究中的最新进展凸显了供体来源的EV在引发同种免疫反应中的关键作用，最终导致移植排斥。移植后，携带供体主要组织相容性复合体（MHC）分子的EV激活受体抗原呈递细胞（APC），引发同种反应性和调节性T细胞反应。虽然免疫抑制药物对于预防排斥至关重要，但它们也可能影响供体细胞中EV的生物发生和释放。本综述探讨了维持性免疫抑制治疗对移植后EV生物发生和释放的影响。此外，EV的释放和摄取可能受特定因素影响，如患者的终末期器官疾病和移植手术本身。使用原代人实质细胞和免疫细胞并结合前沿多组学技术（包括基因组学、蛋白质组学、脂质组学和单EV分析）进行的体外研究，将更深入地了解EV生物学以及免疫抑制药物调节EV引发的免疫过程的机制。详细了解器官衰竭、移植手术和免疫抑制药物如何影响EV生物学，可能会揭示EV在患者免疫激活和调节中的新作用，最终带来改进的免疫抑制策略和更好的移植结果。
