Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Basic and Molecular Epidemiology of Gastrointestinal Disorder Research Center, Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Science, Tehran, Iran.
Int Immunopharmacol. 2018 Jan;54:86-94. doi: 10.1016/j.intimp.2017.11.001. Epub 2017 Nov 4.
Inflammatory bowel disease (IBD) is an autoimmune-inflammatory disorder that results in inflammatory responses in individuals who are genetically susceptible. Uncontrolled inflammation in Crohn's disease (CD) or Ulcerative colitis (UC) affects the patient quality of life. Current therapies are not completely effective while cell therapy, especially the treatment with mesenchymal stem cells (MSCs) absorb lots of attention due to its immunomodulatory properties. So, we examined the effects of mesenchymal stem cells-conditioned medium (MSC-CM) in the experimental model of acute colitis.
MSC-CM was isolated from C57Bl/6 male mice and stored. The acute colitis induction in C57BL/6 mice was performed by dissolving dextran sulfate sodium (DSS) in drinking water and then CM injected intraperitoneally. During the study body weight changes, bleeding, stool consistency, disease activity index (DAI), mortality rate, weight and length of the colon and histopathological analysis were recorded as well as changes in the percentage of Treg cells. The level of IL-17, IL-10, and TGF-β were measured, too. Data were reported as mean±SD and analyzed by One-Way ANOVA test.
Based on the results it is recognized CM inhibited the weight loss and bleeding and improved fecal consistency and DAI. Macroscopic examination of the colon showed that after infusion, colon inflammation was reduced and histopathological analysis showed a decrease in mucosal degeneration. The percentage of Treg cells, secretion of IL-10 and TGF-β was increased while the IL-17 level was reduced.
This study showed that mesenchymal stem cell secretion with immunomodulatory properties has the potential to reduce inflammatory responses.
炎症性肠病(IBD)是一种自身免疫性炎症性疾病,导致遗传易感个体发生炎症反应。克罗恩病(CD)或溃疡性结肠炎(UC)的炎症失控会影响患者的生活质量。目前的治疗方法并不完全有效,而细胞治疗,特别是间充质干细胞(MSCs)的治疗,因其免疫调节特性而引起了广泛关注。因此,我们研究了间充质干细胞条件培养基(MSC-CM)在急性结肠炎实验模型中的作用。
从 C57Bl/6 雄性小鼠中分离 MSC-CM 并储存。通过将葡聚糖硫酸钠(DSS)溶解在饮用水中诱导 C57BL/6 小鼠发生急性结肠炎,然后将 CM 经腹腔内注射。在研究过程中,记录体重变化、出血、粪便稠度、疾病活动指数(DAI)、死亡率、结肠重量和长度以及 Treg 细胞百分比的变化。还测量了 IL-17、IL-10 和 TGF-β 的水平。数据以平均值±标准差表示,并通过 One-Way ANOVA 检验进行分析。
结果表明,CM 抑制了体重减轻和出血,改善了粪便稠度和 DAI。结肠的宏观检查显示,输注后结肠炎症减轻,组织病理学分析显示黏膜变性减少。Treg 细胞百分比、IL-10 和 TGF-β 的分泌增加,而 IL-17 水平降低。
这项研究表明,具有免疫调节特性的间充质干细胞分泌具有减轻炎症反应的潜力。