In vitro functional testing of endothelial progenitor cells that overexpress thrombomodulin.

Published

Journal Article

This study investigated the augmentation of endothelial progenitor cell (EPC) thromboresistance by using gene therapy to overexpress thrombomodulin (TM), an endothelial cell membrane glycoprotein that has potent anti-coagulant properties. Late outgrowth EPCs were isolated from peripheral blood of patients with documented coronary artery disease and transfected with an adenoviral vector containing human TM. EPC transfection conditions for maximizing TM expression, transfection efficiency, and cell viability were employed. TM-overexpressing EPCs had a fivefold increase in the rate of activated protein C production over native EPCs and EPCs transfected with an adenoviral control vector expressing β-galactosidase (p<0.05). TM upregulation caused a significant threefold reduction in platelet adhesion compared to native EPCs, and a 12-fold reduction compared to collagen I-coated wells. Additionally, the clotting time of TM-transfected EPCs incubated with whole blood was significantly extended by 19% over native cells (p<0.05). These data indicate that TM-overexpression has the potential to improve the antithrombotic performance of patient-derived EPCs for endothelialization applications.

Full Text

Duke Authors

Cited Authors

  • Stroncek, JD; Xue, Y; Haque, N; Lawson, JH; Reichert, WM

Published Date

  • August 2011

Published In

Volume / Issue

  • 17 / 15-16

Start / End Page

  • 2091 - 2100

PubMed ID

  • 21466416

Pubmed Central ID

  • 21466416

Electronic International Standard Serial Number (EISSN)

  • 1937-335X

Digital Object Identifier (DOI)

  • 10.1089/ten.TEA.2010.0631

Language

  • eng

Conference Location

  • United States