High-level shear stress stimulates endothelial differentiation and VEGF secretion by human mesenchymal stem cells

Growing experimental evidence suggests that mechanical stimulation play important roles in determining the proliferation, migration, and apoptosis of human mesenchymal stem cells (hMSCs). Here, we show that shear stress stimulates hMSCs toward an EC phenotype in the absence of chemical induction. Most importantly, fluorescence microscopy clearly demonstrated for the first time that the distributions of endothelial-specific markers, vascular endothelial (VE)-cadherin and CD31, in hMSCs were similar to those of ECs at cell-cell adhesion sites after exposing hMSCs to a shear stress of 2 Pa for 2 days with subsequent static culture for 5 days. Western blot analysis proved that shear stress of 2 Pa significantly induced protein expression of von Willebrand factor (vWF), VE-cadherin, and CD31. However, an unclear expression of the endothelial-specific markers was observed in the 0.2 Pa shear stress group. In addition, there was a cumulative production of vascular endothelial growth factor (VEGF), which is known to induce endothelial differentiation of MSCs. By exerting shear stress of 2 Pa on hMSCs for 2 days with subsequent culture for 5 days, the production level of approximately 2-fold compared with that of the control group was achieved. Our findings suggest that high-level shear stress can induce VEGF production and EC differentiation from hMSCs. This may provide a means for addressing the cell sourcing issue for effective tissue engineering.