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J Appl Physiol 95: 2081-2088, 2003. First published July 11, 2003; doi:10.1152/japplphysiol.00232.2003
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Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress

Kimiko Yamamoto,1 Tomono Takahashi,2 Takayuki Asahara,3 Norihiko Ohura,1 Takaaki Sokabe,1 Akira Kamiya,4 and Joji Ando1

1Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, 113-0033 Tokyo; 2Department of Internal Medicine, Tokyo Medical University, 160-8402 Tokyo; 3Department of Physiology, School of Medicine, Tokai University, 259-1193 Isehara; and 4Interdisciplinary Science Center, Nihon University, 102-0074 Tokyo, Japan

Submitted 5 March 2003 ; accepted in final form 1 July 2003

Endothelial progenitor cells (EPCs), circulating in peripheral blood, migrate toward 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, compared with EPCs cultured under static conditions. Shear stress markedly increased the EPC expression of two vascular endothelial growth factor receptors, kinase insert domain-containing receptor and fms-like tyrosine kinase-1, and an intercellular adhesion molecule, vascular endothelial-cadherin, at both the protein and mRNA levels. Assays for tube formation in the collagen gels showed that the shear-stressed EPCs formed tubelike 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.

blood vessels; angiogenesis; neovascularization; mechanical stress; vascular endothelial growth factor


Address for reprint requests and other correspondence: K. Yamamoto, Dept. of Biomedical Engineering, Graduate School of Medicine, Univ. of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033 Tokyo, Japan (E-mail: k-yamamoto{at}umin.ac.jp).




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