Tiam Mana Saffari

206 CHAPTER 9 Considering the overall goal to improve outcomes of decellularized nerve allografts in clinical practice, clinical applicability should be considered when interpretating results. The use of autologous differentiated MSCs requires approximately 4-5 weeks of preparation time, compared to 2-3 weeks for undifferentiated MSCs 16 . Moreover, the costs of the differentiation cocktail required to differentiate MSCs into Schwann cell- like cells are high and add to the costs of extended cell culture. Differences between undifferentiated an differentiated MSCs were not statistically significant in light of the analyzed factors, but undifferentiated MSCs improved functional outcomes of decellularized nerve allografts to a greater extent than differentiated MSCs. Taking all of these factors into consideration, undifferentiated MSCs have the greatest potential for bench-to-bedside application. Hypothetically, at the day of presentation in a clinical setting, adipose tissue can be obtained using minimally invasive techniques from the patient with nerve injury, MSCs can then be derived from this tissue and cultured for approximately two weeks after which the MSCs can be dynamically seeded onto an off-the-shelf commercially available nerve allografts, 12 hours in advance of the nerve repair. Translation to a larger animal model to ensure the enhanced functional outcomes, study of the capacity of human MSCs to be seeded on clinically available nerve allografts and FDA approval are potential hurdles that need to be addressed prior to application of the presented strategy in clinical practice. CONCLUSIONS Undifferentiated and differentiated MSCs significantly improved functional outcomes of decellularized allografts at 12 weeks in motor nerves and equaled the autograft results in the majority of outcome measurements. At 16 weeks, outcome measures normalized as expected. Considering clinical applicability, undifferentiated MSCs are more attractive as outcomes did not significantly differ between both cell-types, and differentiation requires increased time and cost. Acknowledgements We thank Roman Thaler, PhD, for assisting with cell culture and differentiation of the mesenchymal stem cells. We thank Patricia F. Friedrich for assistance with the preparations of the experiments.