Effect of TNF-α 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

Abstract

Aim: The present study aimed to examine the effect of tumor necrosis factor-α (TNF-α) 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 Allen’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-α group (injection with BMSCs under TNF-α treatment at the injured site). Immunochemistry was performed to characterize the culture media after TNF-α-induced differentiation. qRT-PCR and Western blotting analyses were performed to detect the mRNA and protein expression of β-catenin, Wnt3a, GSK-3β 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 β-catenin and Wnt3a mRNA and protein expression was increased, but the GSK-3β and Axin mRNA and protein expression was decreased in the BMSCs + TNF-α group. The SCI rats in the BMSCs + TNF-α group exhibited lower BBB scores, and higher NDSs and BBT scores compared to the BMSCs group. Conclusion: Our study provides evidence that TNF-α inhibition may weaken the ability of BMSCs in neurological functional recovery after SCI by activating the Wnt signaling pathway.

Stem Cell Therapy for Spinal Cord Injury

“…IGF-1 overexpression of BM-MSCs strengthens antioxidant reactions and improves basso mouse scale (BMS) scores 65 . Other approaches, such as modification of the microRNA-124 gene 66 , silencing the Nogo-66 receptor gene 67 , inhibition of tumor necrosis factor α (TNF-α) 68 , and overexpression of neurotrophin-3 (NT-3) 69 , the chemokine stromal-derived factor-1 70 , and neurotrophic factor-derived glial cell (GDNF) genes 71 , exhibited better efficacy than original BM-MSCs in motor function and surrounding axon densities. The effects of individual cell transplantation are enhanced by cotransplantation with cells from other sources.…”

Mitochondrial Transfer from Bone Marrow Mesenchymal Stem Cells to Motor Neurons in Spinal Cord Injury Rats via Gap Junction

“…Epidemiological data indicate that the incidence of SCI is approximately 40.1 cases per million in the United States every year, and males are more likely experience SCI than females 6. Recent studies have demonstrated that stem cell transplantation therapy offers an attractive alternative, especially for bone marrow mesenchymal stem cells (BMSCs) treatment by secreting trophic factors, promoting axonal regeneration and improving neuron survival 7-9. After SCI, the BMSCs have multiple effects on amelioration of immunomodulation and glial scarring 10, 11.…”

Signatures of altered long noncoding RNAs and messenger RNAs expression in the early acute phase of spinal cord injury

“…The early acute phase of SCI can be considered to last from 2 to 48 hr following SCI, and it may play a major part in the development of the secondary injury. At present, however, the detailed molecular mechanisms that underlie the early acute phase of SCI are still incompletely understood (Peng et al, 2017;Y. Zhou, Wang, Li, Li, & Xiao, 2017).…”