miR-210 enhances mesenchymal stem cell-modulated neural precursor cell migration

Abstract

The migration of endogenous neural stem cells and neural precursor cells (NPCs) to sites of injury is essential for neuroregeneration following hypoxic-ischemic events. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential therapeutic source of cells following central nervous system damage; however, few studies have investigated the effects of BMSCs on cell migration. Thus, in the present study, the effects of BMSCs on NPC migration were investigated. In the present study, BMSCs and NPCs were isolated and cultured from mice. The effects of BMSCs on the migration of NPCs were analyzed using a Transwell cell migration assay. BMSCs were transfected with microRNA-210 (miR-210) mimics and inhibitors to examine the effects of the respective upregulation and downregulation of miR-210 in BMSCs on the migration of NPCs. Then, miR-210 expression in BMSCs were quantified and the expression levels of vascular endothelial growth factor-C (VEGF-C), brain derived neurotrophic factor (BDNF) and chemokine C-C motif ligand 3 (CCL3) in the supernatant under hypoxic conditions were investigated via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA. Subsequently, the expression of VEGF-C, BDNF and CCL3 in BMSCs overexpressing miR-210 or BMSCs suppressing miR-210 was examined by RT-qPCR and western blot analyses. BMSCs promoted the migration of NPC, particularly when pre-cultured with BMSCs for 24 h and co-cultured with NPCs for 24 h; the miR-210 expression levels increased under hypoxic conditions. Additionally, the migration of NPCs was also increased when the BMSCs overexpressed miR-210 compared with the BMSCs transfected with a negative control miR and BMSCs with downregulated miR-210 levels. The expression levels of VEGF-C increased in the BMSCs that overexpressed miR-210 and were decreased in BMSCs transfected with a miR-210 inhibitor. The results of the present study indicated that BMSCs promote the migration of NPCs. Overexpression of miR-210 in BMSCs enhanced NPC migration and may be associated with increases in VEGF-C expression levels.