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1 Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
2 Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan
3 Department of Physiology, School of Medicine, Tokai University, Isehara, Japan
4 Interdisciplinary Science Center, Nihon University, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: k-yamamoto{at}umin.ac.jp.
Endothelial progenitor cells (EPCs) circulating in peripheral blood migrate towards target tissue, differentiate and contribute to the formation of new vessels. In this study, we report that shear stress generated by blood flow or tissue fluid flow can accelerate the proliferation, differentiation and capillary-like tube formation of EPCs. When EPCs cultured from human peripheral blood were subjected to laminar shear stress, the cells elongated and oriented their long axes in the direction of flow. The cell density of the EPCs exposed to shear stress was higher and a larger percentage of these cells were in the G2-M phase of the cell cycle, as compared to EPCs cultured under static conditions. Shear stress markedly increased the EPC expression of two vascular endothelial growth factor receptors, KDR and Flt-1, and an intercellular adhesion molecule, VE-cadherin, at both the protein and mRNA levels. Assays for tube formation in the collagen gels showed that the shear-stressed EPCs formed tube-like structures and developed an extensive tubular network significantly faster than the static controls. These findings suggest that EPCs are sensitive to shear stress and that their vasculogenic activities may be modulated by shear stress.
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