Schwann cell-derived exosomes attenuate angiogenesis and fibrotic scar formation and promote nerve repair
Li Xialin1, Hu Guangxun1, Pan Dayu2
1Department of Spinal Surgery, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen 518052, Guangdong Province, China; 2Department of Orthopedics, General Hospital, Tianjin Medical University, Tianjin 300052, China
Abstract: BACKGROUND: Spinal cord injury can result in severe damage to axons and neuronal death, leading to permanent loss of motor and/or sensory function. At present, the treatment methods for spinal cord injury are still very limited. As a non-cellular therapy, exosomes have attracted much attention due to their powerful biological activities, and have the potential to become an emerging treatment option for spinal cord injury.
OBJECTIVE: To investigate the role of Schwann cell-derived exosomes on nerve axons after spinal cord injury in mice.
METHODS: Thirty C57 mice were randomly divided into sham group, Schwann cell-derived exosome treatment group and PBS control group (n=10 per group). The clamp injury was conducted on Schwann cell-derived exosome treatment group and PBS control group. After injury for 24 hours, the mice in the Schwann cell-derived exosome treatment group were injected with exosomes derived from Schwann cells via the caudal vein, and the mice in the PBS control group were injected with PBS via the caudal vein, three times a week for 4 weeks, 25 μL/mice (0.1 g/L) each time. Mice were sacrificed 24 hours after the last injection. After removing the spine, tissue one centimeter above and below the injury site of the spinal cord was isolated for fixation, dehydration, embedding and sectioning. The recruitment of CD31-positive vascular endothelial cells and FSP1-positive fibroblasts in the injured area, as well as the survival of NF200 positive axons was observed by immunofluorescence staining.
RESULTS AND CONCLUSION: Compared with the PBS control group, the number of CD31-positive endothelial cells was decreased (P < 0.01) and the number of FSP1-positive fibroblasts in the injured area was decreased in the mice treated with Schwann cell-derived exosomes (P < 0.05). The number of NF200-positive axons was increased in the Schwann cell-derived exosome treatment group compared with the PBS control group (P < 0.01). These results suggest that Schwann cell-derived exosomes can reduce the recruitment of angiogenesis and scar formation cells in the area after spinal cord injury and promote the recovery of nerve axons.
Key words: spinal cord injury, Schwann cell, exosome, angiogenesis, fibrous scar, axon