Lymphatic endothelial cells-derived exosomes promote axonal regeneration following peripheral nerve injury

doi:10.12307/2023.748

Abstract

Abstract: BACKGROUND: The lymphatic system is involved in the regulation of nerve regeneration. Exosomes have intercellular communication functions and various biological characteristics. Exosomes derived from the lymphatic system have great potential in the treatment of peripheral nerve injury diseases.
OBJECTIVE: To investigate the role and mechanism of lymphatic endothelial cells-derived exosomes on axonal regeneration after peripheral nerve injury.
METHODS: (1) The effect of lymphatic endothelial cells-derived exosomes on the proliferation ability of Schwann cells was detected by EdU cell proliferation assay. (2) Twenty-four male SD rats were randomly divided into three groups with 8 rats in each group, including the sham operation group, peripheral nerve injury group and lymphatic endothelial cells-derived exosomes treatment group. The right sciatic nerves of rat models in the sham operation group were exposed without injury. For the rat models in the peripheral nerve injury group and lymphatic endothelial cells-derived exosomes treatment group, the right sciatic nerves were injected with PBS and lymphatic endothelial cells-derived exosomes under the epineurium of the nerve respectively following sciatic nerve crush. All left sciatic nerves of rats were not treated. The rats in each group were sacrificed 28 days following the operation. The bilateral gastrocnemius muscles were removed to measure the muscle wet-weight ratio. Right sciatic nerves were removed. Histopathological changes and axon arrangement of the sciatic nerve were evaluated by hematoxylin-eosin staining and Masson staining, and axonal regeneration was analyzed by immunofluorescence staining.
RESULTS AND CONCLUSION: (1) Compared with the control group, lymphatic endothelial cells-derived exosomes significantly enhanced the proliferation ability of Schwann cells, and the difference was statistically significant (P < 0.05). (2) At 28 days following the operation, the wet-weight ratio of muscles was significantly higher in the lymphatic endothelial cells-derived exosomes treatment group than that in the peripheral nerve injury group (P < 0.05). Axons in the lymphatic endothelial cells-derived exosomes treatment group were arranged more closely and orderly than those in the peripheral nerve injury group and the axon disintegration and vacuolation caused by injury were less. The NF200 and S100β fluorescence intensities in the lymphatic endothelial cells-derived exosomes treatment group were significantly higher than that in the peripheral nerve injury group, and the difference was statistically significant (P < 0.05). Our findings indicated that lymphatic endothelial cells-derived exosomes could enhance the proliferation ability of Schwann cells to promote axonal regeneration following peripheral nerve injury by elevating the protein expression of NF200 and S100β.

Key words: lymphatic endothelial cell, exosome, Schwann cell, peripheral nerve regeneration, peripheral nerve lymphatic vessel

CLC Number:

Huang Jinsheng, Zhang Geyi, Li Senrui, Li Jiangnan, Lu Laijin, Zhou Nan. Lymphatic endothelial cells-derived exosomes promote axonal regeneration following peripheral nerve injury[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(33): 5314-5319.

Figures/Tables 4

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