The response of human embryonic stem cell-derived endothelial cells to shear stress

Authors

  • Christian M. Metallo,

    1. Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, Wisconsin 53706; telephone: 608-262-8931; fax: 608-262-5434
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  • Maxim A. Vodyanik,

    1. Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
    2. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin
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  • Juan J. de Pablo,

    1. Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, Wisconsin 53706; telephone: 608-262-8931; fax: 608-262-5434
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  • Igor I. Slukvin,

    1. Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
    2. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin
    3. WiCell Research Institute, Madison, Wisconsin
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  • Sean P. Palecek

    Corresponding author
    1. Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, Wisconsin 53706; telephone: 608-262-8931; fax: 608-262-5434
    2. WiCell Research Institute, Madison, Wisconsin
    • Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, Wisconsin 53706; telephone: 608-262-8931; fax: 608-262-5434.
    Search for more papers by this author

Abstract

An important physiological function of vascular endothelial cells is to detect and respond to physical stimuli. While many efforts have been made to derive endothelial cells from human embryonic stem cells (hESCs), the ability of these derivatives to respond to mechanical forces has yet to be ascertained. hESC-derived endothelial cells (hEECs) were obtained by coculturing hESCs with OP9 stromal cells. Here we applied physiologic levels of shear stress to hEECs in a parallel plate flow chamber and observed changes in cell morphology and gene expression, comparing the response to that of human umbilical vein endothelial cells (HUVECs) and human microvascular endothelial cells (HMVECs). Shear induced hEECs to elongate and align in the direction of flow, and their overall transcriptional response to shear was similar to the primary cells tested. In response to shear in hEECs, COX2 and MMP1 were upregulated four- and threefold, MCP1 and VCAM1 expression decreased over fivefold, and ICAM1 and TPA were downregulated almost threefold. TGFβ1 and SOD2 transcription exhibited no change under the conditions tested. Additionally, preshearing of hEECs mitigated TNFα-induced VCAM1 surface expression. These findings suggest that hEECs are capable of functionally responding to changes in fluid shear stress by modulating gene expression and cell morphology. Biotechnol. Bioeng. 2008;100: 830–837. © 2008 Wiley Periodicals, Inc.

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