Vascular Endothelial Growth Factor Enhances Proliferation of Human Tenocytes and Promotes Tenogenic Gene Expression

Background: In obtaining human tenocytes for tendon tissue engineering, a low proliferation rate and phenotype loss during passaging is a problem. It was the authors' aim to evaluate the influence of vascular endothelial growth factor (VEGF) on human tenocyte growth and gene expression. Methods: Human tenocytes were exposed to human VEGF in various concentrations (5, 10, and 20 ng/ml) for 5 days. Cell proliferation was counted and expression of tendon-related genes was analyzed. Results: Tenocyte count was 1.4 x 10(5)/ml, 2.7 x 10(5)/ml, 2.3 x 10(5)/ml, and 3.7 x 10(5)/ml for 0, 5, 10, and 20 ng/ml VEGF, respectively. Expression of Col1 was up-regulated 6.4 4.2-fold, 60.1 +/- 21.6-fold, and 15.8 +/- 10.2-fold for 5, 10, and 20 ng/ml VEGF; all differences were significant with p < 0.05. Col3 was down-regulated to 0.2 +/- 0.1-fold, 0.3 +/- 0.1-fold, and 0.1 +/- 0.03-fold for 5, 10, and 20 ng/ml VEGF; all differences were significant. Eln was up-regulated 2.3 +/- 1.7-fold, 25.5 +/- 10.9-fold, and 16.6 +/- 9.0-fold for 5, 10, and 20 ng/ml VEGF; differences were significant for 10 and 20 ng/ml VEGF. TSC was down-regulated to 0.3 +/- 0.1-fold and 0.3 +/- 0.1-fold for 5 and 20 ng/ml VEGF; differences were significant for 5 and 20 ng/ml. SCX was up-regulated to 31.3 +/- 8.5-fold, 49.1 +/- 23.4-fold, and 20.9 +/- 9.5-fold for 5, 10, and 20 ng/ml VEGF; all changes were significant. Conclusions: VEGF enhances proliferation and expression of tendon-related genes in human tenocytes. It could therefore be a useful addition for tenocyte cultivation.