Femke Mathot

3 MSC-seeding on processed nerve allografts 53 nerve-injury and surgery. In vivo studies demonstrating no differences in functional outcomes compared to undifferentiated MSCs also favor the use of undifferentiated MSCs in the clinical setting. 36, 37 The absence of in vivo differences is potentially caused by the hypothesized limited survivability of differentiated cells 10 or an inefficient delivery of differentiated MSCs. Published delivery methods vary widely, while none of the delivery methods has specifically been tested on differentiated MSCs. Thus, to date there is no compelling evidence for the use of either undifferentiated MSCs or differentiated MSCs for seeded nerve allografts used for segmental motor nerve reconstruction. Figure 4. Undifferentiated MSCs (left) and differentiated MSCs (right) seeded on a nerve allograft. 4a-b. Viable cells are visualized in green, dead cells in red (not present). 4c-f. Scanning Electron Microscopy images of undifferentiated MSCs seeded onto a nerve allograft (left) and differentiated MSCs seeded on a nerve allograft (right) in multiple magnifications (500X, 2000X and 3000X), showing the different morphology of the cells when seeded on the nerve allograft. 4g-h. Cross-sectional images of the mid-portions of processed nerve allografts seeded with undifferentiated (left) and differentiated (right) MSCs. Cell nuclei are Hoechst- stained (bright blue). The inner ultrastructure of the nerve does not contain any cells. Cell-injection and nerve-

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