Tiam Mana Saffari

18 CHAPTER 1 functional recovery of 20-mm nerve gaps reconstructed with decellularized nerve allografts in a rabbit peroneal nerve defect model 39,40 . Decellularization including elastase and cold storage at 4 °C were identified as the optimal conditions and used in subsequent experiments (Figure 4A, rectangle 1). Figure 4A. Flowchart of historical background of this thesis. This thesis is part of an ongoing research line and builds on the results of previously conducted research that has focused on op- timizing a decellularized nerve allograft (rectangle 1) and seeding these allografts with stem cells. With permission of the Mayo Foundation, Copyright Mayo Foundation. All rights reserved. Augmenting decellularized allograft with stem cells Schwann cells are essential within the context of peripheral nerve regeneration after trauma and are crucial during Wallerian degeneration, however, difficult to transplant. The acquisition of autologous Schwann cells requires harvest of large segments of healthy nerve tissue, resulting in donor site morbidities 41,42 . As a result of these limitations, research has been directed towards the use of mesenchymal stem cells (MSC), which are easily accessible, and can be differentiated into Schwann cell-like cells 42 . The importance of MSCs in peripheral nerve regeneration relies on their ability to enhance neurotrophic factors, promote myelin formation and their capacity to be influenced by the microenvironment to differentiate into Schwann cell-like cells 43 . Despite progress in pre-clinical studies, translation to clinical practice is currently limited by many unanswered questions on the application of MSCs in peripheral nerve repair and their interaction with vascularity. Previous research conducted in our research line has focused on individualizing nerve allograft repair by addition of adipose-derived MSCs to the nerve allograft. A new method was described and validated to dynamically seed MSCs on nerve