Tiam Mana Saffari

177 STEM CELLS, VASCULARITY, AND NERVE 8 locally delivered in a hydrogel is feasible, has strong potential to enhance survival of transplanted cells and may be less immunogenic when combined with exosomes. As tissues consist of multiple cell types, potential synergistic therapeutic benefit may occur when multiple stem cell types are administered simultaneously. By combining the properties and secretion of a mixture of neuroregenerative as well as vascular growth factors, cytokines and miRNA, regenerative capacities may be enhanced. Currently, limited data supporting combined cell type administration exist, however, may be promising for future applications 100,101 . The ideal type of stem cell for translation needs to be easily accessible and harvested, proliferate rapidly without carcinogenic consequences, and immune-compatible. Locally delivered cell- based therapy is expected to increasingly take part in enhancing outcomes after nerve reconstruction in the next decades. CONCLUSIONS Improved understanding of the interaction of stem cells and vascularity will provide therapeutic targets to improve outcomes after peripheral nerve reconstruction. The degree of nerve regeneration after PNI is particularly dependent on the local environment of injury and may be altered to promote functional recovery. The microenvironment may be modulated by stem cells and angiogenesis. This topic of interest is complex and involves the secretion of trophic factors that enhance regeneration and revascularization. Revascularization of nerve is suggested to enhance nerve regeneration by organized longitudinally running vessels that provide modeled vessel tracks to precede the repair of damaged nerves. The effect of stem cells, on the other hand, is dependent on their differentiation potential and stimulation by paracrine cues, which are provided by the environment during nerve regeneration. This review discusses the synergistic pathways of stem cells and vascularity and their interaction with nerve following PNI. Despite advancements in well-designed pre- clinical studies, translation of stem cells to clinical practice is currently impeded by ethical issues, risk of tumorigenesis, unknown side-effects and technical challenges. Future research may be shifted towards the use of exosomes, to overcome difficulties associated with the harvest and culture of stem cells. Local modulation of nerve environment is still evolving, and the importance of stem cell and vascularity-based therapies is expected to take a larger part in treatment options of PNIs.