Xue Chunran, Yu Haojun, Pei Xuzhong, Yao Xiaoying, Ding Jie, Wang Xiying, Chen Yi, Guan Yangtai
Department of Neurology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China.
School of Medicine, Shanghai University, Shanghai, 200444, People's Republic of China.
Stem Cell Res Ther. 2025 Feb 7;16(1):51. doi: 10.1186/s13287-025-04187-8.
Human umbilical cord mesenchymal stem cells (hUC-MSCs) have great potential for treating autoimmune diseases for their immunomodulatory and tissue-regenerative abilities; however, their therapeutic role in neuromyelitis optica spectrum disorder (NMOSD) remains uncertain.
10 hUC-MSCs prepared in 200 μl PBS were intravenously administered to a systemic NMOSD model on day 10 and day 14 after immunization. Then, disease progression, immune responses, and blood-brain barrier integrity were evaluated. Additionally, we tested the effects of hUC-MSCs on astrocyte viability and apoptosis using an aquaporin 4 (AQP4) IgG and complement-induced cytotoxicity model in vitro.
hUC-MSCs alleviated NMOSD progression in vivo with improved motor function, reduced inflammatory infiltration, myelin loss, and preservation of astrocytes and neurons. hUC-MSC treatment did not affect autoimmune reactions in the spleen, however, decreased cytokine release in the spinal cord and mitigated blood-brain barrier disruption. Furthermore, in vitro studies revealed that co-culture with hUC-MSCs significantly restored astrocyte viability and reduced apoptosis in AQP4 IgG and complement-mediated damage.
Our results revealed that hUC-MSCs displayed therapeutic efficacy in NMOSD and showed potential in attenuating blood-brain barrier disruption, as well as AQP4 IgG and complement-induced astrocyte apoptosis.
人脐带间充质干细胞(hUC-MSCs)因其免疫调节和组织再生能力在治疗自身免疫性疾病方面具有巨大潜力;然而,它们在视神经脊髓炎谱系障碍(NMOSD)中的治疗作用仍不确定。
在免疫后第10天和第14天,将200 μl PBS中制备的10个hUC-MSCs静脉注射到全身性NMOSD模型中。然后,评估疾病进展、免疫反应和血脑屏障完整性。此外,我们在体外使用水通道蛋白4(AQP4)IgG和补体诱导的细胞毒性模型测试了hUC-MSCs对星形胶质细胞活力和凋亡的影响。
hUC-MSCs在体内减轻了NMOSD的进展,改善了运动功能,减少了炎症浸润、髓鞘损失,并保护了星形胶质细胞和神经元。hUC-MSC治疗不影响脾脏中的自身免疫反应,然而,减少了脊髓中的细胞因子释放并减轻了血脑屏障破坏。此外,体外研究表明,与hUC-MSCs共培养可显著恢复星形胶质细胞活力,并减少AQP4 IgG和补体介导损伤中的细胞凋亡。
我们的结果表明,hUC-MSCs在NMOSD中显示出治疗效果,并在减轻血脑屏障破坏以及AQP4 IgG和补体诱导的星形胶质细胞凋亡方面显示出潜力。