Tiam Mana Saffari

188 CHAPTER 9 ABSTRACT Background Mesenchymal stem cells (MSCs) have the potential to produce neurotrophic growth factors and establish a supportive micro-environment for neural regeneration. The purpose of this study was to determine the effect of undifferentiated and differentiated MSCs dynamically seeded onto decellularized nerve allografts on functional outcomes when used in peripheral nerve repair. Materials and Methods In 80 Lewis rats a ten millimeter sciatic nerve defect was reconstructed with (i) autograft, (ii) decellularized allograft (iii) decellularized allograft seeded with undifferentiated MSCs, or (iv) decellularized allograft seeded with MSCs differentiated into Schwann cell-like cells. Nerve regeneration was evaluated over time by cross sectional tibial muscle ultrasound measurements, and at 12 and 16 weeks by isometric tetanic force measurements (ITF), compound muscle action potentials (CMAP), muscle mass, histology and immunofluorescence analyses. Results At 12 weeks, undifferentiated MSCs significantly improved ITF and CMAP outcomes compared to decellularized allograft alone, while differentiated MSCs significantly improved CMAP outcomes. The autografts outperformed both stem-cell groups histologically at 12 weeks. At 16 weeks, functional outcomes normalized between groups. At both time points, the effect of undifferentiated versus differentiated MSCs was not significantly different. Conclusions Undifferentiated and differentiated MSCs significantly improved functional outcomes of decellularized allografts at 12 weeks and were similar to autograft results in the majority of measurements. At 16 weeks, outcomes normalized as expected. Although differences between both cell-types were not statistically significant, undifferentiated MSCs improved functional outcomes of decellularized nerve allografts to a greater extent and have practical benefits for clinical translation by limiting preparation time and costs.