Laboratory of Veterinary Internal Medicine and Research Institute for Veterinary Science, Department of Clinical Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.
Department of Veterinary Emergency and Critical Care Medicine and Institute of Veterinary Science, College of Veterinary Medicine, Kangwon National University, Chuncheon-si, Republic of Korea.
Sci Rep. 2024 Aug 20;14(1):19273. doi: 10.1038/s41598-024-68853-2.
Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs), specifically those preconditioned with deferoxamine (DFO) in canine adipose tissue-derived MSCs (cAT-MSCs), were explored for treating autoimmune diseases. This study assessed the effects of DFO-preconditioned EVs (EV) in an experimental autoimmune encephalomyelitis (EAE) mouse model. cAT-MSCs were treated with DFO for 48 h, after which EVs were isolated. EAE mice received intranasal EV or EV treatments and were euthanized following histopathologic analysis; RNA and protein expression levels were measured. Histologically, EV and EV groups showed a significant reduction in inflammatory cell infiltration and demyelination. Immunofluorescence revealed increased CD206 and Foxp3 expression, indicating elevated M2 macrophages and regulatory T (Treg) cells, particularly in the EV group. Treg cells also notably increased in the spleen of EV -treated mice. STAT3 and pSTAT3 proteins were upregulated in the EAE groups compared to the naïve group. However, following EV treatment, STAT3 expression decreased compared to the EAE group, whereas pSTAT3 expression was similar in both the EV and EAE groups. In conclusion, EV treatment resulted in reduced STAT3 expression, suggesting its role in T cell regulation and the potential of EV in modulating the STAT3 pathway for reducing inflammation more effectively than non-preconditioned EVs.
间充质干细胞（MSCs）来源的细胞外囊泡（EVs），特别是犬脂肪组织来源的间充质干细胞（cAT-MSCs）经去铁胺（DFO）预处理的 EVs，被探索用于治疗自身免疫性疾病。本研究评估了 DFO 预处理的 EV（EV）在实验性自身免疫性脑脊髓炎（EAE）小鼠模型中的作用。cAT-MSCs 用 DFO 处理 48 小时后，分离 EV。EAE 小鼠接受鼻内 EV 或 EV 治疗，并在进行组织病理学分析后安乐死；测量 RNA 和蛋白质表达水平。组织学检查显示，EV 和 EV 组的炎症细胞浸润和脱髓鞘明显减少。免疫荧光显示 CD206 和 Foxp3 表达增加，表明 M2 巨噬细胞和调节性 T（Treg）细胞增加，特别是在 EV 组中。EV 治疗组的脾脏中 Treg 细胞也明显增加。与正常组相比，EAE 组的 STAT3 和 pSTAT3 蛋白表达上调。然而，与 EAE 组相比，EV 治疗后 STAT3 表达降低，而 EV 和 EAE 组的 pSTAT3 表达相似。总之，EV 治疗导致 STAT3 表达降低，表明其在 T 细胞调节中的作用，以及 EV 在调节 STAT3 通路以更有效地减少炎症方面可能优于非预处理 EV。
