Cellular and Molecular Bioengineering

, Volume 6, Issue 2, pp 220–229 | Cite as

High-level Shear Stress Stimulates Endothelial Differentiation and VEGF Secretion by Human Mesenchymal Stem Cells

  • Lin Yuan
  • Naoya Sakamoto
  • Guanbin Song
  • Masaaki Sato


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.


Mechanical stimulation Cell–cell adhesion Cytokine Immunofluorescence staining 



Vascular endothelial growth factor


Human mesenchymal stem cells


Endothelial cells


Vascular endothelial (VE)-cadherin


von Willebrand factor


Fetal calf serum


Basic fibroblast growth factor


Ethylenediaminetetraacetic acid


Sodium dodecyl sulfate polyacrylamide gel electrophoresis


Ethylene glycol tetraacetic acid


Phenylmethylsulfonyl fluoride


Tris-buffered saline with Tween-20


Horseradish peroxidase



This study was supported in part by Grants-in-Aid for Scientific Research (Specially Promoted Research) from the Japan Society for the Promotion of Science (No. 20001007), the National Natural Science Foundation of China (nos. 30770530, 11032012 and 11102240), the Fundamental Research Funds for the Central Universities (CDJXS11232243), and the Natural Science Foundation Project of CQ CSTC (2010BB5236) of China.


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Copyright information

© Biomedical Engineering Society 2013

Authors and Affiliations

  • Lin Yuan
    • 1
    • 2
  • Naoya Sakamoto
    • 3
  • Guanbin Song
    • 1
  • Masaaki Sato
    • 2
  1. 1.Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of BioengineeringChongqing UniversityChongqingChina
  2. 2.Graduate School of Biomedical EngineeringTohoku UniversitySendaiJapan
  3. 3.Department of Medical TechnologyKawasaki University of Medical WelfareKawasakiJapan

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