Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous system injury

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. Electronic supplementary material The online version of this article (10.1007/s11010-019-03511-0) contains supplementary material, which is available to authorized users.

Improvement of sensory neuron growth and survival via negatively regulating PTEN by miR-21-5p-contained small extracellular vesicles from skin precursor-derived Schwann cells

“…Nonetheless, the regulation effect of EVs on PI3K and more pathways should not be confined in shutting miRs, because several defined lncRNAs have been reported to exert neuroprotective potential [60][61][62], and proteins enriched in SC-derived EVs also could act as bioactive factors once delivered to recipient cells, enhancing proliferation and migration as well as angiogenesis, while negatively regulating apoptosis and oxidative stress [63]. Therefore, more potential of SKP-SC-EVs such as axon guidance, pro-angiogenesis, promoting myelination, and immune inflammation modulation for neuroregeneration microenvironment construction should be further investigated, depending on the genetic and proteomic contents.…”

Schwann cell reprogramming into repair cells increases miRNA-21 expression in exosomes promoting axonal growth

“…In fact, we found that rSC exosomes contained miRNAs that are reported to be involved in diverse functions, including cellular adhesion and modulation of immune activities. Furthermore, a recent proteomic analysis of rSC exosomes showed that they contain proteins associated with different biological processes, including cell adhesion, angiogenesis and immune responses (Wei et al, 2019).…”

Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage

“…Recent findings indicate that microRNAs (miRNAs) carried in exosomes from Schwann cells, macrophages and neurons have a significant impact in the processes that underlie peripheral nerve regeneration [ 176 ]. Proteomic analysis of Schwann cell-derived exosomes revealed the presence of several proteins and signaling pathways that are involved in axon regeneration [ 177 ]. Inflammatory cells appear also to promote the emergence of a growth promoting state in the injured neuron through the release of exosomal NADPH oxidase 2 (NOX2) complexes into the injured axons.…”