3 years ago

Optimising combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice

Søren Overgaard, Chris H. Dreyer, Kristian Kjærgaard, Ming Ding, Nicholas Ditzel, Niklas R. Jørgensen
Introduction: Insufficient blood supply may limit bone regeneration in bone defects. Vascular endothelial growth factor (VEGF) promotes angiogenesis by increasing endothelial migration. This outcome, however, could depend on time of application. Sheep mesenchymal stem cells (MSCs) in severe combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation. Methods: Twenty-eight SCID (NOD.CB17-Prkdcscid/J) mice had hydroxyapatite (HA) granules seeded with 5x105 MSCs inserted subcutaneously. Pellets released VEGF on Days 1-7, Days 1-14, Days 1-21, Days 1-42, Days 7-14, and Days 21-42. After 8 weeks, the implant-bone-blocks were harvested, paraffin embedded, sectioned, and stained with both Haematoxylin Eosin (HE) and immunohistochemistry for human vimentin staining (hVim). Blood samples were collected for determination of bone-related biomarkers in serum. Results: The groups with 5x105 mesenchymal stem cells and VEGF stimulation on Days 1-14 and Days 1-21 showed more bone formation when compared to the control group of 5x105 mesenchymal stem cells alone (p<0.01). Serum biomarkers had no significant values. The hVim staining confirmed the ovine origin of the observed ectopic bone formation. Conclusion: Optimal bone formation of MSCs was reached when stimulating with VEGF during the first 14 or 21 days after surgery. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jbm.a.36195

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