Tiam Mana Saffari

161 STEM CELLS, VASCULARITY, AND NERVE 8 INTRODUCTION Patients with peripheral nerve injuries (PNI) can face severe disability resulting in sensory loss, motor deficits, and neuropathic pain. These deficits may result in a devastating impact on a patient’s quality of life 1 . Despite advancements inmicrosurgical techniques and basic and translational research, surgical reconstruction of PNIs continues to have unsatisfactory clinical outcomes, particularly for reconstructions of major mixedmotor and sensory nerves 2,3 . When end-to-end tension-free neurorrhaphy is not possible, the current gold standard remains reconstruction with autologous cabled nerve graft interposition after excision of the injured nerve stumps. Harvest of autologous nerves faces associated drawbacks, such as permanent donor site morbidity with loss of sensation in the distribution of the harvested nerve 4-7 . Attempts to create a commercially available nerve graft substitute have resulted in a variety of bioabsorbable synthetic conduits or decellularized human allograft nerves. Their clinical efficacy has yet to equal or surpass autologous nerve grafts, especially for defects greater than three centimeters 8 . Engineering of a synthetic substrate for nerve regeneration tomimic the ultrastructure of autologous nerve has been extremely challenging. The use of human allograft fresh nerves for reconstruction requires systemic immunosuppression to prevent graft rejection and is associated with side effects, such as severe opportunistic infections 9,10 . An alternative to fresh human allograft nerves or to engineering a nerve graft is to decellularize and process human allograft nerve. Decellularized allografts serve as a temporary scaffold for regenerating nerve fibers and do not require systemic immunosuppression due to diminished graft rejection potential. Decellularized allografts provide the essential ultrastructural elements and may be pretreated with irradiation, cold preservation, trophic factors, or seeded with Schwann cells or stem cells, to advance outcomes after peripheral nerve reconstruction 4,11 . 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 12 . Specifically, stem cells that have been differentiated into Schwann- like cells, mimicking the function of the original facilitators of axonal regeneration, may enhance neuron survival to improve functional outcomes 4,13 . Growth factors secreted by stem cells may enhance angiogenesis, the sprouting of new capillaries from preexisting ones, to promote revascularization 14-17 .