Exosomes from microRNA 146a overexpressed bone marrow mesenchymal stem cells protect against spinal cord injury in rats.

BACKGROUND:This study aimed to investigate the effect of microRNA 146a (miR-146a) overexpressed bone marrow mesenchymal stem cells (BMMSCs) exosomes on spinal cord injury (SCI) recovery. METHODS:Rat BMMSCs were isolated and transfected with miR-146a mimic (miR-mimic) and control mimic (NC-mimic), after which their exosomes were isolated. Afterward, SCI rat models were constructed, then treated with phosphate buffer saline (PBS), NC BMMSCs exosomes (separated from the culture medium of BMMSCs with NC-mimic), and miR-146a overexpressed BMMSCs exosomes (isolated from the culture medium of BMMSCs with miR-mimic), respectively; additionally, rats underwent sham surgery were treated with PBS as controls. RESULTS:MiR-146a was upregulated in BMMSCs, and BMMSCs derived exosomes post miR-mimic transfection. Then in SCI rats, BMMSCs exosomes elevated the Basso, Beattie, and Bresnahan (BBB) score and reduced hematoxylin&eosin-reflected spinal cord tissue injury. In addition, BMMSCs exosomes did not affect TUNEL positive cells rate while increased NeuN(+) cells/field in spinal cord tissue from SCI rats. As for inflammation, BMMSCs exosomes repressed pro-inflammatory cytokine expressions, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, in spinal cord tissue from SCI rats. Furthermore, miR-146a overexpressed BMMSCs exosomes presented with notably better effects regarding elevating BBB score in SCI rats and reducing tissue injury, neuron apoptosis, and inflammation while enhancing neuron viability in spinal cord tissue from SCI rats. CONCLUSIONS:MiR-146a overexpressed BMMSCs exosomes enhance locomotor capacity and neuron viability while reducing neuron apoptosis and spinal cord tissue inflammation in SCI rats.