Chen Meng, Yu Yang, Yang Shiyao, Yang Deqin
Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, China.
Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China.
Iran J Basic Med Sci. 2021 Aug;24(8):1050-1057. doi: 10.22038/ijbms.2021.56520.12616.
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.
, 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. , 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.
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.
LA may improve the migration ability of MSCs through increasing CXCR4 expression therapy enhancing their therapeutic activity.
结肠炎患病率高,治疗选择有限,亟待解决。单独应用甘草查耳酮A(LA)或rBMMSCs治疗结肠炎有一定效果但有限。本研究旨在制定一种基于LA的策略,通过增加迁移至炎症部位的间充质干细胞(MSCs)数量来提高其对小鼠DSS诱导的结肠炎的治疗能力。
我们将经LA预处理的MSCs、单独的MSCs或PBS注射到结肠炎小鼠的尾静脉中,并在第10天评估结肠长度、疾病活动指数(DAI)评分、体重、组织学活动指数(HAI),并追踪MSCs的位置。我们用小干扰RNA(siRNA)敲低CXCR4基因,然后用LA处理,接着检测CXCR4的mRNA水平以及CXCR4组、CXCR4+LA组、LA组和对照组细胞迁移能力,以验证这种作用与SDF-1-CXCR4信号通路之间的关系。
与MSCs组相比,接受LA预处理的MSCs的小鼠体重减轻得到改善,结肠形态得以保留,DAI和组织学活动指数(HAI)降低。此外,LA+MSCs组迁移至炎症部位的MSCs数量显著增加,CXCR4的表达也显著增加。此外,我们发现LA可以部分纠正由CXCR4-siRNA引起的MSCs迁移减少和CXCR4 mRNA表达降低的情况。
LA可能通过增加CXCR4表达来提高MSCs的迁移能力,从而增强其治疗活性。