Wnt3a Inhibits Inflammatory Responses and Improves Survival in Immortalised Schwann Cells

Background: Spinal cord injury (SCI) triggers a intense inflammatory response that hinders the success of cell transplantation therapies. Immortalised Schwann cells (iSCs) offer a renewable cell source, but their response to inflammation is poorly understood. Wnt3a regulates neural stem cells, but its role in modulating inflammatory responses in iSCs remains unclear.

Methods: Rat Schwann cells (SCs) were immortalised using SV40Tag. An inflammatory model was established by treating iSCs with LPS, in the presence or absence of Wnt3a protein. The inflammatory response, Apoptosis, proliferation, and migration were assessed using quantitative PCR (qPCR), Western blotting, immunofluorescence, CCK-8 assay, TUNEL staining, flow cytometry, and scratch wound healing assay. An acute spinal cord injury model in rats was utilised for in vivo validation.

Results: This study shows that immortalized Schwann cells share some genotypic similarity with primary Schwann cells, but have a much faster proliferation rate than Schwann cells, which can be better used for neurological disease-related research. In addition, in the LPS-induced inflammatory environment, Wnt3a was able to inhibit the expression of IL-1β in immortalized Schwann cells, and enhance the expression of TGF-β by activating NF-κB. More importantly, Wnt3a inhibited the level of Apoptosis in the inflammatory environment and promoted the proliferation and migration ability of cells, which also enhanced the function of immortalized Schwann cells.

Conclusion: Wnt3a modulates the inflammatory response in iSCs, primarily through NF-κB-mediated upregulation of TGF-β, and promotes iSC survival and function. The combination of iSCs and Wnt3a presents a promising strategy for improving cell transplantation therapy for SCI.

NF-κB signaling pathway; Wnt3a; apoptosis; immortalised schwann cells; inflammation; spinal cord injury.