Tiam Mana Saffari

20 CHAPTER 1 Over the past decade, it has been suggested that vascular endothelial cells guide the regeneration of peripheral nerve axons by producing VEGF, and subsequently VEGF became the focus of numerous investigations. Clinical attempts to enhance nerve allografts using VEGF led to conflicting results, suggesting that the specific molecular regulations of angiogenesis following peripheral nerve injury are more complex 51-55 . Prior to implementation of nerve allografts augmented with angiogenesis in the clinical setting, understanding of processes that are necessary for new vessel formation after nerve injury needs to be provided. Augmenting decellularized allograft with stem cells and angiogenesis combined Stem cell-based therapy may offer a suitable treatment with several regenerative benefits to restore neuronal function, including supporting remyelination and revascularization of the affected organ 43 . Blood vessels, on the other hand, have been postulated to be a systemic source of stem cells in regenerating tissues secondary to their vascular origin 56 . Studies that investigate the potential synergistic effects of blood supply and stem cell delivery are lacking. To this end, the experimental approach in this thesis has been to augment decellularized nerve allografts with angiogenesis and stem cells combined. PROJECT OBJECTIVE AND HYPOTHESIS The objective of this thesis is to enhance peripheral nerve regeneration in nerve allografts to meet outcomes of nerve autografts by augmenting the nerve injury site with angiogenesis and stem cells (Figure 4C). This thesis’ hypothesis is that augmentation of nerve allograft environment with angiogenesis and stem cells improves nerve regeneration and revascularization.