Exosomes Derived From miR-133b-Modified Mesenchymal Stem Cells Promote Recovery After Spinal Cord Injury

Dysregulation of microRNAs (miRNAs) has been found in injured spinal cords after spinal cord injury (SCI). Previous studies have shown that miR-133b plays an important role in the differentiation of neurons and the outgrowth of neurites. Recently, exosomes have been used as novel biological vehicles to transfer miRNAs locally or systemically, but little is known about the effect of the delivery of exosome-mediated miRNAs on the treatment of SCI. In the present study, we observed that mesenchymal stem cells, the most common cell types known to produce exosomes, could package miR-133b into secreted exosomes. After SCI, tail vein injection of miR-133b exosomes into rats significantly improved the recovery of hindlimb function when compared to control groups. Additionally, treatment with miR-133b exosomes reduced the volume of the lesion, preserved neuronal cells, and promoted the regeneration of axons after SCI. We next observed that the expression of RhoA, a direct target of miR-133b, was decreased in the miR-133b exosome group. Moreover, we showed that miR-133b exosomes activated ERK1/2, STAT3, and CREB, which are signaling pathway proteins involved in the survival of neurons and the regeneration of axons. In summary, these findings demonstrated that systemically injecting miR-133b exosomes preserved neurons, promoted the regeneration of axons, and improved the recovery of hindlimb locomotor function following SCI, suggesting that the transfer of exosome-mediated miRNAs represents a novel therapeutic approach for the treatment of SCI.