Reduced inflammatory cell recruitment and tissue damage in spinal cord injury by acellular spinal cord scaffold seeded with mesenchymal stem cells.

Abstract

Therapy using acellular spinal cord (ASC) scaffolds seeded with bone marrow stromal cells (BMSCs) has previously been shown to restore function of the damaged spinal cord and improve functional recovery in a rat model of acute hemisected spinal cord injury (SCI). The aim of the present study was to determine whether BMSCs and ASC scaffolds promote the functional recovery of the damaged spinal cord in a rat SCI model through regulation of apoptosis and immune responses. Whether this strategy regulates secondary inflammation, which is characterized by the infiltration of immune cells and inflammatory mediators to the lesion site, in SCI repair was investigated. Basso, Beattie, and Bresnahan scores revealed that treatment with BMSCs seeded into an ASC scaffold led to a significant improvement in motor function recovery compared with treatment with an ASC scaffold alone or untreated controls at 2 and 8 weeks after surgery (P<0.05). Two weeks after transplantation, the BMSCs seeded into an ASC scaffold significantly decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, as compared with the ASC scaffold only and control groups. These results suggested that the use of BMSCs decreased the apoptosis of neural cells and thereby limited tissue damage at the lesion site. Notably, the use of BMSCs with an ASC scaffold also decreased the recruitment of macrophages (microglia; P<0.05) and T lymphocytes (P<0.05) around the SCI site, as indicated by immunofluorescent markers. By contrast, there was no inhibition of the inflammatory response in the control and ASC scaffold only groups. BMSCs regulated inflammatory cell recruitment to promote functional recovery. However, there was no significant difference in IgM-positive expression among the three groups (P>0.05). The results of this study demonstrated that BMSCs seeded into ASC scaffolds for repair of spinal cord hemisection defects promoted functional recovery through the early regulation of inflammatory cell recruitment with inhibition of apoptosis and secondary inflammation.