Tiam Mana Saffari

164 CHAPTER 8 mostly quiescent and are activated in response to injury 28 . The close vicinity of these progenitor cells to the circulation allows for their mobilization to the region of interest to facilitate a number of processes including tissue regeneration 29 . Differentiation of mesenchymal stem cells (MSC) into Schwann-like cells enhances the secretion of various angiogenic factors, including angiopoietin-1 and VEGF-A, resulting in enhanced angiogenic potency and neurite outgrowth 17,30 . MSCs differentiated into Schwann-like cells specifically, have been shown to increase revascularization of nerve allografts after in vivo reconstruction of sciatic nerve defects in rats 31 . Revascularization of nerve and neural regeneration Following PNI, axons and myelin degenerate distally to the injury site by interactions of Schwann cells and macrophages in a process known as Wallerian degeneration 32,33 . During regeneration, blood vessels precede axonal extension and serve as tracks for Schwann cells to migrate and guide axonal growth, suggesting an interdependence between neurite outgrowth and vascularity 34,35 . VEGF is central to the control of angiogenesis and critical in the process of maturation and stabilization of vessels 36,37 . In addition to stimulating the outgrowth of Schwann cells and blood vessels, VEGF also enhances axonal outgrowth from dorsal root ganglia 38 . It has been proposed that VEGF improves hematopoietic stem cell survival by an internal autocrine loop mechanism 38,39 . This mechanism implies that it is not accessible for extracellular inhibitors, such as antibodies, to block this loop and proposes that the VEGF-dependent loop is solely generated in stem cells and not in endothelial cells 39 . VEGF had become the focus of numerous basic science studies and was used to augment nerve grafts. However, it was found that the angiogenic effect of VEGF did not translate into enhanced motor recovery 40 , suggesting that the role of vascularity in nerve regeneration does not depend on one element solely, but is broader and more complex 24 . Recent research investigated the effect of an adipofascial vascularized flap on nerve revascularization in nerve allografts using novel microcomputed imaging. These results suggest that revascularization patterns follow longitudinal inosculation, the growth of host vessels from nerve coaptation ends, occurring primarily from proximal, rather than from both nerve ends, as previously believed 41,42 . Organized longitudinally running vessels provide modeled vessel tracks to precede the repair of damaged nerves 14,16,23,24 .