Tiam Mana Saffari

204 CHAPTER 9 DISCUSSION Despite advances in decellularization techniques for allograft nerves, nerve autograft remain the gold standard for segmental defect reconstruction of critical motor or sensory nerves 1,6 . To overcome the limitations of decellularized allograft nerves, MSCs have been hypothesized to improve outcomes of decellularized allograft nerves 7 by producing proteins and cytokines that establish a micro-environment favorable for neural regeneration 8,12-14,37 . Differentiated MSCs have been demonstrated to exert their neurotrophic effect immediately after implementation by expressing increased levels of neurotrophic genes, while undifferentiated MSCs require additional time to interact with the surrounding tissue prior to expressing neurotrophic genes 14 . The purpose of this study was to determine the effect of dynamically seeding undifferentiated and differentiated MSCs onto decellularized nerve allografts 7 with respect to functional and histologic outcomes in a rat sciatic defect model, in order to determine which cell- type has greatest clinical potential. In this study, MSCs were successfully differentiated into Schwann cell-like cells 16 and dynamically seeded onto decellularized nerve allografts 27 . Compared to unseeded allografts, undifferentiated MSCs led to significant improvement of both ITF and CMAP (P=0.017 and P=0.004) outcomes at 12 weeks, while differentiated MSCs only led to significant improved CMAP outcomes (P<0.001). These findings correspond to the study of Hou and colleagues whom observed that (differentiated) MSC-seeded grafts recovered earlier than acellular grafts when measuring electrophysiology, with significant results at 12 weeks 38 . Differences between groups normalized at 16 weeks which is consistent with the study of Tang and colleagues, demonstrating normalizing ITF measurements at 16 weeks of follow-up 39 . Functional assessment did not result in any significant differences between both cell-types for all functional outcome measures at 12 and 16 weeks, which is in line with published studies of Orbay and Watanabe 22,23 . The hypothesized consequences of different effective phases of both cell-types could not be confirmed in this study. At 16 weeks, no significant differences in functional outcomes between groups were found, except for muscle mass recovery that was significantly better in autografts than in allografts seeded with differentiated MSCs (P=0.002). Although muscle mass is easily obtainable, it is an indirect measurement of motor outcome as enlarged muscle