Tiam Mana Saffari

256 CHAPTER 12 and endothelial cells can be activated towards myofibroblasts to participate in the formation of nerve fibrosis. Angiogenesis was recognized in slowing down the differentiation towards pro-fibrotic myofibroblasts. In SIEF rats, an increased T helper population (CD4 + cells) was found after one week postoperatively in peripheral blood, indicating that immune reactive changes could be detected peripherally. The use of flowcytometry to detect peripheral T cells in blood samples is feasible and could be expanded to multiple time points and a larger set of immune cells to provide a broader evaluation of the short-term immune reaction. The results presented in Chapter 7 show that augmentation of decellularized nerve allografts with angiogenesis improves early functional recovery in a rat sciatic nerve defect model. The mechanisms directing towards this result are twofold. First, the SIEF flap increases vascularity which precedes nerve regeneration. Enhanced vascularity in the nerve graft was measured using micro CT, photography (Chapter 5), gene expression levels, immunohistochemical staining (Chapter 6) and immunofluorescence (Chapter 7). Second, the SIEF flap diminishes nerve fibrosis, leading to enhanced nerve regeneration. This is supported by analyzed collagen deposition levels (Chapter 6) and the fact that an improved N-ratio was found in SIEF compared to allograft only (Chapter 7). A well vascularized bed, provided by the SIEF flap, not solely improves revascularization, but is also suggested to decrease graft ischemic time, subsequently impeding necrosis. PART II: THE CONTRIBUTION OF ANGIOGENESIS AND STEM CELLS IN NERVE REGENERATION In Part II, the contribution of angiogenesis and stem cells in nerve regeneration has been investigated, represented by Chapter 8-10. In Chapter 8 , a review on the interaction of stem cells and vascularity in peripheral nerve regeneration is provided. Stem cells can be acquired through various sources that correlate to their differentiation potential, including embryonic stem cells, neural stem cells, and mesenchymal stem cells (MSC). Each source of stem cells serves its particular differentiation potential and properties associated with the promotion of revascularization and nerve regeneration. The effect of stem cells is dependent on paracrine cues provided by the environment during nerve regeneration. Despite advancements in pre-clinical studies, translation of stem cells application to clinical practice is currently limited by ethical issues, culture technique