Wu Junfeng, Li Anqi, Shi Yu, Wang Yanping, Luo Jingyu, Zhuang Wei, Ma Xiaoru, Qiao Zhixin, Xiu Xin, Lang Xiujuan, Zhang Sifan, Liu Xijun, Sun Bo, Li Hulun, Liu Yumei
Department of Neurobiology, Harbin Medical University, Harbin, China.
Department of Neurobiology, Harbin Medical University, Harbin, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Harbin, China.
Int Immunopharmacol. 2025 Jan 27;146:113853. doi: 10.1016/j.intimp.2024.113853. Epub 2024 Dec 19.
Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) have shown therapeutic potential in experimental autoimmune encephalomyelitis (EAE). As a non-invasive method of drug administration, intranasal delivery is anticipated to emerge as a novel option for the treatment of central nervous system (CNS) disorders. Therefore, this study aims to treat EAE by nasal exosomes and explore its specific mechanism, especially its impact on the blood-brain barrier (BBB).
BMSCs-Exos were isolated and characterized. An EAE model was then established, and these exosomes were administered intranasally to the mice. Changes in body weight and clinical scores were monitored following treatment to assess the efficacy. Additionally, inflammatory infiltrates and demyelination in the CNS were evaluated, alongside the quantification of expression levels of BBB-related adhesion molecules and tight junction (TJ) proteins.
Intranasal delivery of BMSCs-Exos ameliorates the severity of EAE disease, reducing inflammatory infiltration in the CNS and demyelination in the spinal cord. This treatment did not influence the differentiation of T cells in the spleen. Furthermore, the nasal delivery of BMSCs-Exos enhances the integrity of TJs in the cerebral cortex and spinal cord, as well as inhibiting the expression of adhesion molecules. These exosomes promote the expression of TJ-related markers in bEnd3 cells, including ZO-1, Occludin, and Claudin 5. At the same time, they suppress the expression of adhesion molecule-related markers, such as ICAM1 and VCAM1.
Our study suggests that intranasal administration of BMSCs-Exos significantly reduces inflammatory infiltration and demyelination in the CNS of EAE mice. Furthermore, this treatment does not influence the differentiation of T cells in the spleen. Additionally, nasal reinfusion of BMSCs-Exos can improve the integrity of the BBB in EAE mice.
骨髓间充质干细胞来源的外泌体（BMSCs-Exos）已在实验性自身免疫性脑脊髓炎（EAE）中显示出治疗潜力。作为一种非侵入性给药方法，鼻内给药有望成为治疗中枢神经系统（CNS）疾病的新选择。因此，本研究旨在通过鼻内给予外泌体治疗EAE，并探索其具体机制，尤其是其对血脑屏障（BBB）的影响。
分离并鉴定BMSCs-Exos。然后建立EAE模型，并将这些外泌体经鼻给予小鼠。治疗后监测体重和临床评分的变化以评估疗效。此外，评估中枢神经系统中的炎症浸润和脱髓鞘情况，同时定量血脑屏障相关黏附分子和紧密连接（TJ）蛋白的表达水平。
经鼻给予BMSCs-Exos可改善EAE疾病的严重程度，减少中枢神经系统中的炎症浸润和脊髓中的脱髓鞘。这种治疗不影响脾脏中T细胞的分化。此外，经鼻给予BMSCs-Exos可增强大脑皮质和脊髓中TJ的完整性，并抑制黏附分子的表达。这些外泌体促进bEnd3细胞中TJ相关标志物的表达，包括ZO-1、闭合蛋白和Claudin 5。同时，它们抑制黏附分子相关标志物的表达，如ICAM1和VCAM1。
我们的研究表明，经鼻给予BMSCs-Exos可显著减少EAE小鼠中枢神经系统中的炎症浸润和脱髓鞘。此外，这种治疗不影响脾脏中T细胞的分化。此外，经鼻回输BMSCs-Exos可改善EAE小鼠血脑屏障的完整性。
