Administration of MicroRNA-210 Promotes Spinal Cord Regeneration in Mice

Study Design. Experimental animal study of treatment of spinal cord injury (SCI). Objective. To investigate the therapeutic effects of administering microRNA-210 (miR-210) to promote angiogenesis in a mouse SCI model. Summary of Background Data. Despite many previous studies regarding SCI, there is no established treatment in clinical practice. miRNAs have attracted immense attention because of their crucial role in human disease, and they have been proposed as potential new therapeutic targets for SCI. Methods. At specific times after administration, mice were analyzed by several methods to examine the distribution of miR-210, histological angiogenesis and neurogenesis, functional recovery from SCI, and the expression levels of target genes of miR-210. Results. After injection of miR-210 into the lesion of the injured spinal cord, expression of endogenous miR-210 increased until 6 days after injection. The administration of miR-210 promoted angiogenesis and astrogliosis, and improved functional recovery after SCI compared with the noninjected controls. Furthermore, the area made up of axons and myelin in the spinal cord tissues caudal to the injury site was larger in mice injected with miR-210 than those of the controls. Apoptotic cell death was lower in mice administered miR-210. After administration of miR-210, the expressions of protein-tyrosine phosphate 1B and ephrin-A3, both gene targets of miR-210, were downregulated at the protein level and protein-tyrosine phosphate 1B expression was also downregulated at the transcriptional level. Conclusion. MiR-210 might contribute to spinal cord repair by promoting angiogenesis via the inhibition of protein-tyrosine phosphate 1B and ephrin-A3.