Ruan Guang-Feng, Zheng Ling, Huang Jia-Shu, Huang Wan-Xue, Gong Bang-Dong, Fang Xing-Xing, Zhang Xiao-Yu, Tang Jian-Ping
Department of Rheumatology, Tongji Hospital of Tongji University, Shanghai 200065, P.R. China.
Department of Respiratory Medicine, Tongji Hospital of Tongji University, Shanghai 200065, P.R. China.
Exp Ther Med. 2017 Jun;13(6):2828-2838. doi: 10.3892/etm.2017.4313. Epub 2017 Apr 6.
Mesenchymal stem cells (MSCs) serve immuno-regulatory functions and offer a promising novel treatment for certain autoimmune diseases. The present study investigated the therapeutic effect of mice bone marrow (BM)-MSCs on mice with relatively late stage of Sjögren-like disease and the impact of BM-MSCs on the microRNA (miRNA) expression profiles of splenic CD4+ T cells. Female NOD/Ltj mice were randomized into two groups: The disease group (n=8) and the MSC-treated group (n=8). Female ICR mice served as the healthy control group (n=8). The MSC-treated group received an injection of MSCs when they were 26 weeks old. Water intake, blood glucose and salivary flow rate were measured and submandibular glands were resected and stained with hematoxylin and eosin to calculate the focus score. The concentrations of interleukin (IL)-2, IL-6, hepatocyte growth factor, interferon γ, IL-10, prostaglandin E2, transforming growth factor β1 and tumor necrosis factor-α in serum were measured using ELISA. The expression of miRNAs in splenic CD4+ T cells were measured using deep sequencing. The results demonstrated that treatment with BM-MSCs prevented a decline in the salivary flow rate and lymphocyte infiltration in the salivary glands of NOD mice, indicating that MSC-treatment had a therapeutic effect on NOD mice with relatively late stage of Sjögren-like disease. ELISA and deep sequencing results showed that the three groups of mice had different serum concentrations of cytokines/growth factors and different miRNA expression profiles of splenic CD4+ T cells. This implies that the alteration in serum levels of cytokines/growth factors and miRNA expression profiles of splenic CD4+ T cells may explain the therapeutic effect MSCs have on Sjögren's syndrome.
间充质干细胞（MSCs）具有免疫调节功能，为某些自身免疫性疾病提供了一种有前景的新型治疗方法。本研究调查了小鼠骨髓（BM）-MSCs对类干燥综合征相对晚期小鼠的治疗效果以及BM-MSCs对脾CD4+ T细胞微小RNA（miRNA）表达谱的影响。雌性NOD/Ltj小鼠被随机分为两组：疾病组（n = 8）和MSC治疗组（n = 8）。雌性ICR小鼠作为健康对照组（n = 8）。MSC治疗组在26周龄时接受MSCs注射。测量饮水量、血糖和唾液流速，并切除下颌下腺，用苏木精和伊红染色以计算灶性评分。使用酶联免疫吸附测定法（ELISA）测量血清中白细胞介素（IL）-2、IL-6、肝细胞生长因子、干扰素γ、IL-10、前列腺素E2、转化生长因子β1和肿瘤坏死因子-α的浓度。使用深度测序测量脾CD4+ T细胞中miRNA的表达。结果表明，BM-MSCs治疗可防止NOD小鼠唾液流速下降和唾液腺淋巴细胞浸润，表明MSC治疗对类干燥综合征相对晚期的NOD小鼠具有治疗作用。ELISA和深度测序结果显示，三组小鼠血清中细胞因子/生长因子浓度不同，脾CD4+ T细胞的miRNA表达谱也不同。这意味着细胞因子/生长因子血清水平的改变和脾CD4+ T细胞的miRNA表达谱可能解释了MSCs对干燥综合征的治疗作用。
