Femke Mathot

General introduction 21 1 seed human MSCs on human nerve grafts or on clinically available nerve substitutes and to analyze their gene expression profiles after seeding; hopefully setting the stage for clinical application somewhere in the near future. As preliminary step for the other chapters, the current knowledge on differentiation of MSCs into Schwann cell-like cells is summarized in chapter 2 . It sets the fundament of why differentiated MSCs deserve to be studied in the perspective of peripheral nerve repair, besides undifferentiated MSCs. The ability of differentiated MSCs to be dynamically seeded onto processed nerve allografts like undifferentiated MSCs is examined and described in chapter 3 , enabling a fair comparison of the in vitro and in vivo potential of both cell types. Gene expression profile changes of differentiated and undifferentiated MSCs after seeding on nerve allografts, affected by the extracellular matrix of the nerve allograft, are studied at various time points after seeding in chapter 4 . As revascularization is hypothesized to be an essential factor for successful nerve regeneration, we first tested and validated new evaluation strategies for nerve vascularization in chapter 5 . In chapter 6 , this is extrapolated to an in vivo study in which the level of vascularization in nerve allografts seeded with differentiated and undifferentiated MSCs is quantified and compared to the vascularization of unseeded allografts, autografts and normal nerves. The potential of differentiated and undifferentiated stem cell seeding to improve functional outcomes after peripheral nerve repair is studied in a rat sciatic nerve defect model in chapter 7 . Functional results of MSC-seeded nerve allografts are compared to unseeded allografts and autografts over time and at two long term end points. To translate the described strategies to a more clinically applicable model, the study in chapter 8 focuses on the potential of human MSCs to be seeded onto clinically available nerve graft substitutes. The consequences of the interaction between the MSCs and the extracellular matrix of the nerve graft substitutes on a gene expression level are studied and described in chapter 9 . In chapter 10 , the acquired results of all chapters are related to each other, discussed and placed in a broader perspective. An English and a Dutch summary are provided in chapter 11 .