Femke Mathot

4 Interaction between MSCs and a nerve allograft 73 an decellularized nerve allograft. 7 The validated dynamic seeding strategy that ensures the atraumatic delivery of viable MSCs on the surface of processed allografts is an additional strength of this study. 37, 38 As indicated above, the in-vitro set up should first be translated to an in-vivo model to confirm the stimulatory effects of different MSC states on peripheral nerve regeneration. A repetition of the current study with human undifferentiated and differentiated MSCs with clinically available nerve graft substitutes (collagen conduits or decellularized allograft nerve) would be a logical next step for clinical translation. CONCLUSION Differentiation of MSCs in Schwann cell-like cells changes their baseline gene expression profile. The gene expression profile of both differentiated MSCs and undifferentiated MSCs changes when the MSCs interact with the ECM of a decellularized nerve allograft after being dynamically seeded on their surface. Differentiated MSCs are likely to play a major role on the short-term nerve regeneration by expressing high gene-levels in the first 72 hours after seeding, while the effect of undifferentiated MSCs appears a week after seeding. The differences in gene-profile and effective phases suggests that both cell-types can affect nerve regeneration in different ways and at different time points. Acknowledgements We thank Patricia F. Friedrich for assistance with the preparations of the experiments, as well as the members of the Shin, Bishop and van Wijnen laboratories for stimulating discussions, as well as generous sharing of ideas and reagents. Funding This study was funded by the NIH R01 NS102360. None of the authors has a conflict of interest.

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