Mechanisms of the immunomodulation effects of bone marrow-derived mesenchymal stem cells on facial nerve injury in SD rats

Mechanisms of the immunomodulation effects of bone marrow-derived mesenchymal stem cells on facial nerve injury in SD rats
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骨髓间充质干细胞对SD大鼠面神经损伤的免疫调节作用机制

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期刊:
immunomodulation, mesenchymal stem cells (MSCs), facial nerve, motor neurons
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通讯作者:
Robert Chunhua Zhao 赵春华
Robert Chunhua Zhao 赵春华
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其他
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作者:
Yining Ge 葛怡宁;Yongli Zhang 张永丽;Qi Tang 唐琦;Juanjuan Gao 高娟娟;Hua Yang 杨华;Zhiqiang Gao 高志强;Robert Chunhua Zhao 赵春华

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正常的面神经功能对人类来说是非常重要的。然而,如果损伤,FN功能很难完全恢复。近年来,许多研究报道了干细胞的免疫调节功能。然而,SCs对FN损伤的免疫调节作用尚不清楚。本研究旨在探讨SD大鼠骨髓间充质干细胞(BMSCs)对FN损伤的免疫调节机制,特别是对Th17的调节以及BMSCs对中枢面运动神经元(FMN)的保护作用。首先,收集大鼠FN。将FN与BMSCs共同或单独培养,用ELISA法检测培养上清液中转化生长因子-β-1、IL-6、肝细胞生长因子、诱导型一氧化氮合酶和前列腺素E_2的水平。采用大鼠FN损伤模型,观察局部注射或不注射BMSCs治疗后大鼠颈淋巴结内Th17细胞比例的变化。此外,在大鼠FN损伤模型中,研究了骨髓间充质干细胞与非骨髓间充质干细胞对FMN的凋亡指数。我们发现骨髓间充质干细胞在培养过程中能够分泌高水平的IL-6、肝细胞生长因子、前列腺素E_2、诱导型一氧化氮合酶和转化生长因子-β-1。骨髓间充质干细胞治疗组小鼠颈部LN Th17细胞百分率明显低于对照组。骨髓间充质干细胞处理组的FMN的凋亡指数明显低于对照组。结论:骨髓间充质干细胞可以独立分泌细胞因子IL-6、肝细胞生长因子、前列腺素E_2、诱导型一氧化氮合酶和转化生长因子-β-1,这些细胞因子可以调节T细胞亚群之间的平衡,并通过抑制神经元的凋亡来保护FMN。
Normal facial nerve (FN) function is very important for human being. However, if injured, FN function is difficult to restore completely. Recently, many studies reported the immune regulation function of stem cells (SCs). However, the immunomodulation function of SCs on FN injury is still unclear. Our study aims to explore the mechanism of immunomodulation effect of SD rat bone marrow-derived stem cells (BMSCs) on FN injury and specially focus on the regulation of Th17 and the protection effects of BMSCs on central facial motor neurons (FMNs). First, rat FNs were harvested. FN and BMSCs were cultured together or separately and levels of TGF-β1, IL-6, HGF, iNOS and PGE2 in supernatant were detected by ELISA. Then, after treating with or without local BMSCs injection, the proportion of Th17 in neck lymph nodes (LNs) were investigated in rat FN injury models. Further, the apoptotic index of FMNs was studied in rat FN injury models which were treated with or without BMSCs. We found that BMSCs could secrete high levels of IL-6, HGF, PGE2, iNOS and TGF-β1 in culture. The percentage of Th17 of neck LNs in BMSCs-treated group was significantly lower than that in the control group. The apoptotic index of FMNs in BMSCs-treated group was significantly lower than that in the control group. In conclusion, our research indicates BMSCs could independently secrete cytokines IL-6, HGF, PGE2, iNOS, and TGF-β1, and these cytokines could regulate the balance among subsets of CD4+ T cells and could protect FMNs by inhibiting neuron apoptosis.