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The Therapeutic Efficacy of Adipose Tissue-Derived Mesenchymal Stem Cell Conditioned Medium on Experimental Colitis Was Improved by the Serum From Colitis Rats
Frontiers in Bioengineering and Biotechnology ( IF 5.7 ) Pub Date : 2021-09-17 , DOI: 10.3389/fbioe.2021.694908
Li-Li Qi 1 , Zhe-Yu Fan 1 , Hai-Guang Mao 1 , Jin-Bo Wang 1
Affiliation  

Adipose derived mesenchymal stem cells (AD-MSCs) have shown therapeutic potential in treatments of inflammatory bowel disease (IBD). Due to the harsh host environment and poor survival of the cells, controversy concerning the homing, proliferation and differentiation of MSCs in lesion tissue still remains. It has been reported that conditioned media from MSCs could improve the colitis, whereas the therapeutic efficiency could be significantly elevated by the stimulation of pro-cytokines. In this study, we pre-treated the adipose derived MSCs with the serum from colitis rats and then the activated conditioned media (CM-AcMSC) were collected. To compare the therapeutic effects of CM-MSC and CM-AcMSC on IBD, we constructed dextran sodium sulphate (DSS)-induced colitis rat models. The colitis was induced in rats by administrating 5% DSS in drinking water for 10 days, and the disease symptoms were recorded daily. The colon histopathological changes were observed by different staining methods (H&E and PAS). The expression levels of MUC2 and tight junctions (TJs) were determined by RT-qPCR. The levels of inflammatory cytokines were analyzed by ELISA and western blot analysis. Our findings suggested that CM-AcMSC was more effective in ameliorating the clinical features and histological damage scores. Treatment with CM-AcMSC significantly increased the expression of MUC2 and TJs and suppressed the production of pro-inflammatory cytokines in colonic tissues of colitis rats. The inhibitory effects of CM-AcMSC on inflammatory responses of colitis rats were mediated by NF-κB signaling pathway. These results suggested that pre-activation of MSCs with serum from colitis rats could promote the production of paracrine factors and improve the therapeutic effects of conditioned medium on colitis rats.



中文翻译:

来自结肠炎大鼠的血清提高了脂肪组织来源的间充质干细胞条件培养基对实验性结肠炎的治疗效果

脂肪来源的间充质干细胞 (AD-MSCs) 在炎症性肠病 (IBD) 的治疗中显示出治疗潜力。由于宿主环境恶劣,细胞存活率低,关于MSCs在病变组织中的归巢、增殖和分化的争议仍然存在。据报道,来自 MSCs 的条件培养基可以改善结肠炎,而通过刺激前细胞因子可以显着提高治疗效率。在这项研究中,我们用来自结肠炎大鼠的血清预处理了脂肪来源的 MSC,然后收集了活化的条件培养基 (CM-AcMSC)。为了比较 CM-MSC 和 CM-AcMSC 对 IBD 的治疗效果,我们构建了葡聚糖硫酸钠 (DSS) 诱导的结肠炎大鼠模型。通过在饮用水中给予5% DSS 10天在大鼠中诱发结肠炎,并且每天记录疾病症状。通过不同的染色方法(H&E和PAS)观察结肠组织病理学变化。通过 RT-qPCR 测定 MUC2 和紧密连接 (TJ) 的表达水平。通过ELISA和蛋白质印迹分析分析炎性细胞因子的水平。我们的研究结果表明,CM-AcMSC 在改善临床特征和组织学损伤评分方面更有效。用 CM-AcMSC 治疗显着增加了 MUC2 和 TJs 的表达,并抑制了结肠炎大鼠结肠组织中促炎细胞因子的产生。CM-AcMSC对结肠炎大鼠炎症反应的抑制作用是通过NF-κB信号通路介导的。

更新日期:2021-09-17
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