Effect of TNF-?± Inhibition on Bone Marrow-Derived Mesenchymal Stem Cells in Neurological Function Recovery after Spinal Cord Injury via the Wnt Signaling Pathway in a Rat Model

摘要

>Aim: The present study aimed to examine the effect of tumor necrosis factor-?± (TNF-?±) inhibition on bone marrow-derived mesenchymal stem cells (BMSCs) in neurological function recovery after spinal cord injury (SCI) via the Wnt signaling pathway in a rat model. Methods: The rat model of SCI was established using Allena€?s method. Seventy-two adult male Sprague Dawley (SD) rats were randomly assigned into 4 groups (18 rats in each group): the sham control group, saline control group, BMSCs group (injection with BMSCs at the injured site) and BMSCs + TNF-?± group (injection with BMSCs under TNF-?± treatment at the injured site). Immunochemistry was performed to characterize the culture media after TNF-?±-induced differentiation. qRT-PCR and Western blotting analyses were performed to detect the mRNA and protein expression of ?2-catenin, Wnt3a, GSK-3?2 and Axin. The Basso Beattie Bresnahan (BBB) locomotor score, neurological deficit score (NDS), and balance beam test (BBT) score were used to assess neurological functional recovery of SCI rats. Results: In the BMSC group, numerous spherical cell clusters grew in suspension, and the cells were nestin-, NF200- and GFAP-positive. Compared with the sham control and BMSC groups, the ?2-catenin and Wnt3a mRNA and protein expression was increased, but the GSK-3?2 and Axin mRNA and protein expression was decreased in the BMSCs + TNF-?± group. The SCI rats in the BMSCs + TNF-?± group exhibited lower BBB scores, and higher NDSs and BBT scores compared to the BMSCs group. Conclusion: Our study provides evidence that TNF-?± inhibition may weaken the ability of BMSCs in neurological functional recovery after SCI by activating the Wnt signaling pathway.