Combining miR-23b exposure with mesenchymal stem cell transplantation enhances therapeutic effects on EAE
Combining miR-23b exposure with mesenchymal stem cell transplantation enhances therapeutic effects on EAE
复制标题
将 miR-23b 暴露与间充质干细胞移植相结合可增强 EAE 的治疗效果
DOI：
10.1016/j.imlet.2020.11.007
复制
发表时间：
2021-01-01
影响因子：
4.4
通讯作者：
Liu, Xijun
中科院分区：
文献类型：
--
作者：
Hu, Ruixue;Lv, Weiqi;Liu, Xijun
骨髓间充质干细胞（BMSCs）具有免疫调节能力，可改善自身免疫性疾病，如多发性硬化症（MS）、系统性红斑狼疮和类风湿性关节炎。然而，骨髓间充质干细胞介导的免疫抑制可能难以实现。BMSC移植的疗效可以通过辅助治疗来增强。在这里，我们证明了用过表达microRNA (miR)-23b的骨髓间充质干细胞治疗实验性自身免疫性脑脊髓炎（EAE）（一种多发性硬化模型）的小鼠，比用传统骨髓间充质干细胞治疗具有更好的协同作用和更长期的治疗效果。过表达miR-23b可增强骨髓间充质干细胞抑制Th17细胞分化和减少IL-17分泌的能力。与传统的骨髓间充质干细胞相比，过表达miR-23b的骨髓间充质干细胞（miR23b-BMSCs）分泌的肿瘤生长因子β 1 （tgf - β 1）增强，tgf - β 1是一种促进调节性T （Treg）细胞分化的细胞因子。病理上，miR23b-BMSC移植延缓了EAE的进展，显然是通过降低Th17/Treg细胞比例和抑制炎症细胞穿过血脑屏障的浸润，从而减缓脊髓脱髓鞘。这些结果可能会使骨髓间充质干细胞更好地用于自身免疫性疾病的治疗。
Bone marrow mesenchymal stem cells (BMSCs) have the immuno-modulatory capacity to ameliorate autoimmune diseases, such as multiple schlerosis (MS), systemic lupus erythematosus and rheumatoid arthritis. However, BMSC-mediated immunosuppression can be challenging to achieve. The efficacy of BMSC transplantation may be augmented by an adjuvant therapy. Here, we demonstrated that treatment of mice with experimental autoimmune encephalomyelitis (EAE), a model of MS, with BMSCs over-expressing microRNA (miR)-23b provided better synergistic and longer-term therapeutic effects than treatment with traditional BMSCs. Over-expression of miR-23b enhanced the ability of BMSCs to inhibit differentiation of Th17 cells and reduced IL-17 secretion. Compared to traditional BMSCs, the miR-23b over-expressing BMSCs (miR23b-BMSCs) exhibited enhanced secretion of tumor growth factor beta 1 (TGF-beta 1), a cytokine that promotes the differentiation of regulatory T (Treg) cells. Pathologically, miR23b-BMSC transplantation delayed EAE progression, apparently by reducing the Th17/Treg cell ratio and inhibiting inflammatory cell infiltration across the blood-brain barrier, and thus slowing spinal cord demyelination. These results may lead to better utility of BMSCs as a treatment for autoimmune diseases.