Effect of bone marrow mesenchymal stem cells modified with miR-155 on immunoregulation

Abstract

Objective To specifically alter the expression level of microRNA-155 (miR- 155) in bone marrow-derived mesenchymal stem cells (BMSC), we investigate the effect of BMSCs on immunoregulation by inducing dendritic cells (DC) after the expression of miR-155 was changed in MSCs. Methods The experiment was divided into CON, miR-155 agomir NC, miR- 155 agomir, miR-155 antagmir NC and miR-155 antagomir groups. DCs were induced for 48 hours by coculture with BMSCs transfect with difference miR-155 and then the maturation and migration of DC was detected. Further, the induced DCs were co-cultured with T cells for 72 hours to detect T cell proliferation. One-way ANOVA (and non-parametric) was used for statistical analysis among groups and t tests were used for statistical analysis between two groups. Results Flow cytometric visualization showed that the proliferation of T cells was decreased in the miR-155 agomir group. The expression level of CD40, the surface markers of DC maturation decreased from 100% to 85%(t = 33.71, P < 0.05) after the expression of miR-155 was increased, and the expression of CD86 decreased from 100% to 75% (t = 57.00, P < 0.05). Meanwhile BMSCs overexpressed with miR- 155 decrease the migratory ability of DCs (t = 7.35, P < 0.01). The expression of NF-κβ signaling pathway proteins in DCs induced by BMSCs was significantly decreased (t = 23.32, P < 0.05) after the expression of miR-155 was increased in BMSCs; and the expression of AKT signaling pathway proteins was significantly decreased (t = 22.21, P < 0.05). Conclusion By inducing DC, BMSCs highly expressed with miR-155 decreased the proliferation of T cells. The high expression level of miR-155 enhances the immunosuppressive capacity of BMSCs. Key words: MicroRNA155; Bone marrow derived mesenchymal stem cells; Dendritic cells; Immunoregulation