Tiam Mana Saffari

245 GENERAL DISCUSSION 11 of newly formed vessels are equally important to facilitate axonal outgrowth. The use of stem cells in peripheral nerve regeneration holds significant promise as these cells have the ability to respond to appropriate stimuli in their microenvironment, resulting in enhanced motor outcomes. Augmentation of nerve allografts with undifferentiated MSCs results in longitudinally running vessels along the entire length of the nerve graft, providing guidance for axon growth. In contrast, differentiated MSCs lead to a mesh network of non-organized microvessels in the nerve, possibly lacking this guidance. Although current evidence explaining their cellular interaction with nerve and vascularity during regeneration remains insufficient, practical considerations lean towards the use of undifferentiated MSCs. Aforementioned possible pathways for further nerve regeneration research are provided to enhance mechanistic understanding during the process of nerve regeneration and to achieve results with allografts comparable to nerve autografts. FUTURE PERSPECTIVES AND RESEARCH Numerous important questions regarding the cellular interactions in vivo remain: What is the exact number of stem cells needed to exert a beneficial effect? What is the optimal route of stem cell administration and does the provision of vascularity actually prolong the viability of stem cells? These unanswered questions are contributing to the fact why stem cell nerve research is still ongoing and its application has yet to make headways into clinical practice. Some may have the same arising question: will this ever happen? Science is beautifully complex and not all breakthroughs in basic science will eventually be clinically relevant or feasible. However, they do expand our mechanistic understanding of complex biological processes. The key elements of successful nerve regeneration are fibrocytes, Schwann cells and vascularity. Finding these three elements, or their substitution, in a fine balance remains a challenge. I believe that the results provided in this thesis serve as a stepping stone towards new insights. The interaction between stem cells, vascularity and nerve regeneration is depicted in Figure 2 and hypothesizes how these factors interact to eventually lead to enhancing nerve regeneration of nerve allografts. Currently, few studies have addressed the interaction of stem cells and vascularity in nerve regeneration, which creates an opportunity for elucidating its synergistic pathways in future research.