Tiam Mana Saffari

257 SUMMARY / SAMENVATTING 12 challenges and risk of tumorgenesis. To overcome the difficulties associated with the harvest of stem cells, delay in culture and high costs of stem cells, future research could be directed towards the use of exosomes. In Chapter 9 , the outcomes of stem cell seeding onto decellularized nerve allografts in a rat sciatic nerve defect model are provided. The main finding was that seeding of nerve allografts with both undifferentiated MSCs and MSCs differentiated into Schwann cell-like cells resulted in improved functional outcomes. Seeding with undifferentiated MSCs leads to a significant increase in force. It is hypothesized that stem cells promote a tolerogenic cellular paracrine environment for nerve allografts, resulting in the stimulation of neurotrophic and angiogenic growth factors, ultimately leading to enhanced functional recovery. Undifferentiated MSCs and MSCs differentiated into Schwann cell-like cells each exert different interactions with the surrounding microenvironment leading to their individual stem cell secretome over time. When taken preparation time, costs and achieved effect on functional recovery into account, undifferentiated MSCs have more potential for future research in peripheral nerve reconstruction. In Chapter 10 , the combined effect of angiogenesis and stem cells on microvascular architecture of decellularized nerve allografts was evaluated in a rat sciatic nerve defect model. Vascular volume was measured using micro CT and spatial distribution analysis was used to evaluate volume and diameter of vessel segments. These distributions were enhanced in nerve allografts augmented with angiogenesis and further improved when angiogenesis was combined with MSCs. The greatest increase of vascular volume, size of vessels and revascularization of the mid-section of the nerve allograft was found when angiogenesis was combined with undifferentiated MSCs. This combination is hypothesized to work synergistically resulting in organized longitudinally running vessels that provide modeled vessel tracks to precede the repair of damaged nerves. In Chapter 11 , the results of this thesis are discussed in light of current literature. Furthermore, possible pathways for further nerve regeneration research are provided. After nerve injury, vascular endothelial cells guide the regeneration of peripheral nerve axons by producing vascular endothelial growth factor (VEGF). This process is induced by hypoxia and stimulates a cascade of pathways. A well vascularized bed stimulates a