Femke Mathot

9 MSC gene expression on nerve substitutes 155 Figure 5. Gene expression curve of MSCs seeded onto Avance® Nerve Grafts and NeuraGen® Nerve Guides concerning the immunoglobulin marker CD96 at 6 different time points after seeding. Error bars = Standard error of the mean DISCUSSION Secondary to their regenerative ability, MSCs are of broad biomedical relevance. 56-62 While differentiation of MSCs into specific cell types (i.e. differentiation into Schwann type cells) has been described as one mode of action 63, 64 , secretion of essential trophic factors is a functionally different and possible more plausible explanation for their regenerative capacities. 14, 16, 65, 66 This putative tissue-specific trophic expression of MSCs occurs in response to cues from their micro-environment. 18, 67, 68 In this study, gene expression profiles of human MSCs seeded onto Avance® Nerve Grafts and NeuraGen® Nerve Guides were examined over time in order to provide mechanistic insight in the interaction of MSCs seeded on nerve substitutes. Expression curves of a select panel of prominent neurotrophic, myelination, angiogenic, ECM and cell surface marker/immunoglobulin genes have been analyzed. The displayed gene expressions of seeded MSCs are all expressed as a ratio of the gene expression in unseeded MSCs, the reference group. Considering a gene expression ratio of 1.0 meaning that the interaction between MSCs and the nerve substitutes did not result in changes in gene expression, one could argue that the interaction of MSCs with the Avance® Nerve Grafts leads to a clear upregulation in the first hours to days after seeding of neurotrophic genes NGF, GDNF and BDNF, myelination markers PMP22, MPZ and angiogenic genes CD31 and VEGF-a. In the long term, the interaction between MSCs and the Avance® Nerve Grafts causes an upregulation of BDNF, VEGF-a and COL1A1. The interaction between MSCs and the NeuraGen® Nerve Guide led on the short term to an upregulation of neurotrophic genes NGF, GDNF and BDNF, myelination markers PMP22 and MPZ, angiogenic genes CD31 and VEGF-a, ECM gene COL1A1 and cell surface marker CD96. In the long term, the expression of neurotrophic genes GDNF and BDNF,