Abstract
This study aimed to assess the efficacy of Quality and Quantity media-cultured mononuclear cells (QQ-MNCs) for promoting nerve regeneration in a mouse sciatic nerve transection model. Human peripheral blood mononuclear cells (PB-MNCs) and QQ-MNCs derived from healthy volunteers were used/compared. The left sciatic nerve was surgically transected in 27 mice. After complete nerve transection was confirmed, end-to-end direct epineurial nerve repair was performed using 9-0 nylon. Fibrin glue was applied to the tissue around the injury site to limit diffusion of the study treatment followed by application of 0.5 ml phosphate buffered saline (PBS) or PB-MNCs (2x106 cells) or QQ-MNCs (2x106 cells) to the injury site. The skin was then closed using 6-0 nylon. Histomorphology, immunohistochemistry, electrophysiologic examination, and functional assessment were evaluated at 12-weeks followed by euthanasia and subsequent harvesting of the left sciatic nerves and the left and right gastrocnemius muscles for examination. QQ-MNCs mice exhibited significant improvement in all histomorphologic parameters (axon fiber diameter, myelin thickness, percentage of nerve density) and immunohistochemistry assays (S100, SOX10, GFAP, neurofilament, IL-1β, VEGF, anti-HNA, TNF-α, vWF) compared to PBS mice (all p < 0.05). QQ-MNCs mice also had a significantly higher Basso Mouse Scale score compared to PBS mice (p = 0.018). The percentage of nerve density adjacent to the injury site was significantly higher in QQ-MNCs mice than in PB-MNCs mice (p = 0.049). IL-1β expression was significantly lower in QQ-MNCs mice than in PB-MNCs mice (p = 0.01). QQ-MNCs mice demonstrated significantly better functional and histomorphologic outcomes of nerve regeneration compared to PB-MNCs mice and PBS mice.