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

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 ۱۰. In vitro, we knocked down the CXCR۴ gene by siRNA and then treated it with LA, then tested the mRNA level of CXCR۴ and the migration ability of group CXCR۴, CXCR۴+LA, LA, and control to verify the relationship between this effect and the SDF-۱-CXCR۴ 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 CXCR۴ significantly increased too. Furthermore, we found that LA could partly revise the decrease of the migration of MSCs and the expression of CXCR۴ mRNA caused by CXCR۴-siRNA.Conclusion: LA may improve the migration ability of MSCs through increasing CXCR۴ expression therapy enhancing their therapeutic activity.

Keywords:

Colitis , CXCR۴ , inflamation , Licochalcone A , Mesenchymal stem cells