Candidate Gene Identification: SOX11 Downregulation and IL-7Upregulation Correlate with the Pro-Proliferative Effect of MesenchymalStem Cell-Derived Exosomes on Schwann Cells

INTRODUCTION/BACKGROUND: Schwann cell (SC) proliferation is crucial for repairing peripheral nerve injuries (PNIs), and mesenchymal stem cell-derived exosomes (MSCs-Exos) show promise in treating PNIs. METHODS: The characterization process was performed by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. SCs were co-cultured with menstrual blood-derived MenSCs-Exos to assess their proliferation through CCK-8 assay and flow cytometry. RNA-Seq was utilized to identify differentially expressed genes (DEGs) linked to SC proliferation. DEGs were subjected to GSEA and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, the overexpression of SOX11 and the knockout of IL-7 were carried out, and the functions of SOX11 and IL-7 were verified using the CCK8 assay and flow cytometry. RESULTS: MenSCs exhibited osteogenic and adipogenic differentiation potential, and MenSCs-Exos demonstrated typical exosomal characteristics. These exosomes were efficiently internalized by SCs, promoting their proliferation and cell cycle progression. RNA-Seq identified 113 differentially expressed genes (DEGs) (60 upregulated and 53 downregulated) in Schwann cells (SCs) treated with MenSCs-derived exosomes (MenSCs-Exos) relative to the untreated control group. After excluding DEGs that were also altered in the MenSCs-conditioned medium (CM) group, 18 unique DEGs specific to the MenSCs-Exos treatment were further identified. qRT-PCR and Western blot showed notably upregulated IL22RA2 and IL-7 expression and a reduction in SOX11 level. Further knockout and overexpression experiments confirmed that downregulation of SOX11 and the upregulation of IL-7 might be related to the proliferative-promoting effect of MSCs-Exos on Schwann cells. DISCUSSION: MenSCs-Exos can be efficiently internalized by SCs and significantly promote their proliferation and cell cycle progression by upregulating IL-7 and downregulating SOX11. This suggests that MenSCs-Exos may enhance SCs' proliferative capacity and repair ability through this molecular mechanism. CONCLUSION: This study confirms the therapeutic potential of MenSCs-Exos in promoting neural regeneration, identifies key genes and pathways regulating Schwann cell proliferation, thereby providing novel molecular targets and experimental evidence for further elucidation of exosome-mediated repair mechanisms.