Publication date: Available online 9 May 2019
Source: Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Nadia Rbia, Liselotte F. Bulstra, Eric A. Lewallen, Steven E.R. Hovius, Andre J. van Wijnen, Alexander Y. Shin
Summary
Mesenchymal stromal cells (MSCs) secrete many soluble growth factors and have previously been shown to stimulate nerve regeneration. MSC seeded processed nerve allografts could potentially be a promising method for large segmental motor nerve injuries. Further progress in our understanding of how the functions of MSCs can be leveraged for peripheral nerve repair is required before clinical translation can be made. The present study therefore investigated whether interactions of adipose-derived MSCs with decellularized nerve allografts can improve gene- and protein expression of growth factors that may support nerve regeneration. Human nerve allografts (n=30) were decellularized and seeded with undifferentiated human adipose-derived MSCs. Subsequently, the MSCs and MSC seeded grafts were isolated at days 3, 7, 14 and 21 days in culture for RNA expression analysis by qRT-PCR. Evaluated genes included NGF, BDNF, PTN, GAP43, MBP, PMP22, VEGF and CD31. Growth factor production was evaluated and quantified using Enzyme-Linked Immunosorbent Assay (ELISA). Over 21 days, semi-quantitative RT-PCR analysis showed that adherence of MSCs to nerve allografts significantly enhances mRNA expression of neurotrophic, angiogenic, endothelial and myelination markers (e.g., BDNF, VEGF, CD31 and MBP). ELISA analysis revealed an upregulation of BDNF and reduction of both VEGF and NGF protein levels. This study demonstrates that seeding of undifferentiated adipose-derived MSCs onto processed nerve allografts permits the secretion of neurotrophic and angiogenic factors that can stimulate nerve regeneration. These favorable molecular changes suggest that MSC supplementation of nerve allografts may have potential in improving nerve regeneration.
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