Pretreatment with licochalcone a enhances therapeutic activity of rat bone marrow mesenchymal stem cells in animal models of colitis.

Pretreatment with licochalcone a enhances therapeutic activity of rat bone marrow mesenchymal stem cells in animal models of colitis.
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甘草查耳酮a预处理增强大鼠骨髓间充质干细胞在结肠炎动物模型中的治疗活性

DOI:
10.22038/ijbms.2021.56520.12616
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发表时间:
2021-08
影响因子:
2.2
通讯作者:
Yang D
Yang D
中科院分区:
医学4区
文献类型:
--
作者:
Chen M;Yu Y;Yang S;Yang D

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目的(S):结肠炎患病率高,治疗选择有限,亟待解决。利可酮A(LA)或rBMMSCs单独应用治疗结肠炎有一定但有限的效果。本研究旨在开发一种基于LA的策略,通过增加间充质干细胞(MSCs)迁移到炎症部位的数量来提高MSCs对DSS诱导的结肠炎的治疗能力。材料和方法:在体内,将经LA、MSCs或PBS预处理的MSCs注入结肠炎小鼠尾静脉,测量结肠长度、疾病活动指数(DAI)评分、体重、HAI评分,并在第10天追踪MSCs的位置;体外,用siRNA敲除CXCR4基因,然后用LA处理,检测CXCR4的mRNA水平以及CXCR4组、CXCR4+LA组、LA组和对照组的迁移能力,以验证这一作用与SDF-1-CXCR4信号通路的关系。结果:与MSCs组相比,经LA处理的MSCs组小鼠体重减轻,结肠形态保持不变,DAI和组织学活动指数(HAI)降低。此外,LA+MSCs组向炎症部位迁移的MSCs数量明显增加,fifi表达也明显增加。此外,我们还发现LA可以部分纠正CXCR4-siRNA引起的MSCs迁移减少和CXCR4基因表达的减少。结论:LA可能通过增加CXCR4的表达,增强MSCs的治疗活性,从而改善MSCs的迁移能力。
Objective(s): Colitis has a high prevalence rate, limited treatment options, and needs to be solved urgently. Application of Licochacone A (LA) or rBMMSCs alone in the treatment of colitis has a certain but limited effect. This study aims to develop an LA-based strategy to improve mesenchymal stem cells’ (MSCs’) therapeutic capacity in mice DSS-induced colitis by increasing the number of MSCs migrating to the inflammation site. Materials and Methods: In vivo, we injected MSCs pretreated with LA, MSCs alone, or PBS into the tail vein of colitis mice, and assessed the colon length, disease activity index (DAI) score, body weight, HAI score, and tracked the location of MSCs at day 10. In vitro, we knocked down the CXCR4 gene by siRNA and then treated it with LA, then tested the mRNA level of CXCR4 and the migration ability of group CXCR4, CXCR4+LA, LA, and control to verify the relationship between this effect and the SDF-1-CXCR4 signaling pathway. Results: The mice that received LA- pretreated MSCs had ameliorated body weight loss, preserved colon morphology, and decreased DAI and histological activity index (HAI) compared with the MSCs group. Besides, the number of MSCs migrating to the inflammation site significantly increased in group LA+MSCs, and expression of CXCR4 significantly increased too. Furthermore, we found that LA could partly revise the decrease of the migration of MSCs and the expression of CXCR4 mRNA caused by CXCR4-siRNA. Conclusion: LA may improve the migration ability of MSCs through increasing CXCR4 expression therapy enhancing their therapeutic activity.
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