Abstract
Exosomes are nanometer-sized vesicles involved in intercellular communication, and they are released by various cell types. To learn about exosomes produced by Schwann cells (SCs) and to explore their potential function in repairing the central nervous system (CNS), we isolated exosomes from supernatants of SCs by ultracentrifugation, characterized them by electron microscopy and immunoblotting and determined their protein profile using proteomic analysis. The results demonstrated that Schwann cell-derived exosomes (SCDEs) were, on average, 106.5 nm in diameter, round, and had cup-like concavity and expressed exosome markers CD9 and Alix but not tumor susceptibility gene (TSG) 101. We identified a total of 433 proteins, among which 398 proteins overlapped with the ExoCarta database. According to their specific functions, we identified 12 proteins that are closely related to CNS repair and classified them by different potential mechanisms, such as axon regeneration and inflammation inhibition. Gene Oncology analysis indicated that SCDEs are mainly involved in signal transduction and cell communication. Biological pathway analysis showed that pathways are mostly involved in exosome biogenesis, formation, uptake and axon regeneration. Among the pathways, the neurotrophin, PI3K-Akt and cAMP signaling pathways played important roles in CNS repair. Our study isolated SCDEs, unveiled their contents, presented potential neurorestorative proteins and pathways and provided a rich proteomics data resource that will be valuable for future studies of the functions of individual proteins in neurodegenerative diseases.
Highlights
Central nervous system (CNS) injury, such as spinal cord injury and brain injury, causes irreversible loss of motor and sensory function [1, 2]
This study provides new evidence that Schwann cell-derived exosomes (SCDEs) may act as a novel therapeutic strategy for CNS injury
The results showed that CD9 and Alix, which are exosome markers, could be detected, but TSG101 was not (Fig. 2c), which is consistent with exosome characteristics [18]
Summary
Central nervous system (CNS) injury, such as spinal cord injury and brain injury, causes irreversible loss of motor and sensory function [1, 2]. Due to the development of modern society, the occurrence rate of CNS damage increases year by year. The predicament of CNS regeneration is always attributed to the poor regenerative plasticity of mature neurons as well as the detrimental microenvironment caused by the lesion [3]. The peripheral nervous system (PNS) exhibits adequate regeneration after injury, which is different from the CNS. During this process, glial cells in situ play a more important role than functional neurons. In the PNS, Schwann cells promote nerve regeneration through secreting
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