Efficacy of Quality and Quantity media-cultured mononuclear cells for promoting peripheral nerve regeneration in mouse model

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.