Femke Mathot

Chapter 9 156 angiogenic genes CD31 and VEGF-a, ECM genes COL1A1, COL3A1 and FBLN1 and cell surface marker CD96 were all upregulated by the interaction between the MSCs and the NeuraGen® Nerve Guide. Genes of which the expression was downregulated for both groups were PTN, GAP43 and LAMB2. A summary of the described gene expression trends and differences is displayed in table 2 . The described steps of Wallerian degeneration and axon regeneration in which the evaluated genes are hypothetically involved are illustrated in figure 6 . It displays the proposed mechanism of MSC-seeding; MSCs are seeded on the outer surface, gene expression of the MSCs is changed by the ECM, resulting in production of trophic factors that are involved in Wallerian degeneration and axon regeneration inside the nerve substitutes. Table 2. Summary of interaction-induced relative changes in gene expression of human MSCs on the short and long term. The signs under significance display whether there were significant differences between the groups at the first two (directly and 24 hours after seeding, separated by a forward slash) and the final two (14 days and 21 days after seeding, separated by a forward slash) time points. ↑↑↑ = extreme enhancement ↑↑ = moderate enhancement, ↓↓ = moderate reduction ↑ = slight enhancement, ↓ = slight reduction ≈ = no enhancement, no reduction - = no significant difference, * = p<0.05, **=p<0.01, ***=p<0.001 Gene ID Biology Short term (0 - 24 hours) Long term (14 - 21 days) Avance® NeuraGen® Significance Avance® NeuraGen® Signifi- cance NGF Neurotrophic marker ↑↑ ↑↑ *** / ** ↓↓ ↓↓ - / - GDNF Neurotrophic marker ↑↑ ↑↑ - / - ≈ ↑↑ - / - PTN Neurotrophic marker ↓↓ ↓↓ - / - ↓↓ ≈ * / *** GAP43 Neurotrophic marker ↓↓ ↓↓ - / - ↓ ↓ - / - BDNF Neurotrophic marker ↑ ↑↑ - / - ↑↑ ↑↑ * / - PMP22 Myelination marker ↑ ↑ - / - ≈ ≈ - / - MPZ Myelination marker ↑ ↑ - / - ↑ ↑ - / - VEGF-a Angiogenic marker ↑↑ ↑↑↑ * / - ↑↑ ↑↑↑ - / * PECAM/ CD31 Angiogenic marker ↑ ↑ - / - ↓ ↑ - / - COL1A1 ECM protein ≈ ↑ ** / - ↑ ↑ - / - COL3A1 ECM protein ≈ ↑ - / - ≈ ↑ - / *** FBLN1 ECM protein ↓ ≈ - / - ↓ ↑ * / *** LAMB2 Extracellular matrix protein ↓ ↓ - / - ↓ ↓ - / - CD96 Cell surface marker / immunoglobulin ↑ ↑ - / - ≈ ↑ - / -