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The response of human embryonic stem cell‐derived endothelial cells to shear stress
Author(s) -
Metallo Christian M.,
Vodyanik Maxim A.,
de Pablo Juan J.,
Slukvin Igor I.,
Palecek Sean P.
Publication year - 2008
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.21809
Subject(s) - embryonic stem cell , umbilical vein , microbiology and biotechnology , endothelial stem cell , stromal cell , stem cell , shear stress , biology , mmp1 , downregulation and upregulation , cell , immunology , gene expression , chemistry , gene , cancer research , materials science , in vitro , genetics , composite material
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.