Tiam Mana Saffari

244 CHAPTER 11 longitudinally running vessels that provide modeled vessel tracks to precede the repair of damaged nerves 53,55,65,66 . Contemplating the above mentioned results, I could argue which subtype of MSCs is most beneficial for nerve regeneration. While differentiated MSCs specifically, have been shown to improve revascularization when seeded onto nerve allografts 59 , the effect of undifferentiated MSCs is more evident in enhancing motor recovery. This may put my hypothesis that revascularization leads to improved motor recovery in question. However, no evidence regarding the in vivo secretome of undifferentiated MSCs compared to differentiatedMSCs seeded onto nerve allografts has been available, making it difficult to understand the interaction of these cells with nerve in the rat model. Second, due to the lack of a high resolution micro CT scanner, these results were found using conventional photography at 16 weeks 59 . This 2D method lacks information regarding the interconnectivity of the vascular tree and solely considers a 16 week time point, limiting our understanding of the vessel organization over time. Third, seeding of nerve allografts with differentiated MSCs led to a mesh network of non-organized microvessels in the nerve 59 . This is in line with results found in Chapter 10. Concluding from prior results presented in this thesis, organized vessels may precede growing axons while non-aligned vessels may lack this guidance function. More research is needed to understand how the augmentation of nerve allograft with stem cells has led to enhanced motor outcomes at 12 weeks and to tie these in with our findings prior to drawing conclusions. In reality, considering the prolonged culture time and higher costs of differentiated MSCs 67,68 , the fact that differentiated MSCs are not proven superior to undifferentiated MSCs and that the latter results in an enhanced motor recovery to a greater extent, I believe that undifferentiated MSCs are more desirable for clinical application. CONCLUSIONS The results from this thesis have expanded our mechanistic understanding of revascularization of nerve and provide evidence for the use of vascularized adipofascial flaps to enhance nerve allograft outcomes. The ability of vasculature to provide a niche for stem cells, which are activated in response to injury, suggests that blood vessels are more widely involved in tissue regeneration than was previously appreciated. Not solely the amount of vascularity is of importance, but the distribution and direction