Femke Mathot

2 Stem cell differentiation in peripheral nerve repair 31 inflammatory response after nerve-injury. A dual function, in which a small fraction of the MSCs has a structural function by replacing injured tissue-cells, while the remaining part of the MSCs maximizes the intrinsic regenerative capacity of the injured tissue by producing growth factors and cytokines, is not inconceivable. The described different functions of MSCs are shown in figure 1 . In light of the hypotheses for the mechanisms of action of MSCs, several key questions need to be addressed prior to clinical implementation. These include the role of differentiation of MSCs prior to administration, the optimal dosing and time frame of application of differentiated versus undifferentiated MSCs and how MSCs need to be administered regardless of differentiation status. APPLICATION OF MSCS An important aspect for the clinical application of MSCs is that outside factors like local anesthetics or contrast medium can influence the viability of MSCs and should be taken into account in studies on the potential of MSCs for clinical applications. 19, 20 Although the outcomes of preclinical and clinical research on the use of MSCs have been promising in a wide variety of clinical disciplines, further research to determine the optimal doses and time points of implantation, the long-term risks and the long-term efficacy are needed to optimize outcomes of MSC-supported tissue regeneration. 21, 22 Figure 1. Schematic overview of the (hypothesized) subset of functions of mesenchymal stromal cells.