In vitro functional testing of endothelial progenitor cells that overexpress thrombomodulin.
Journal Article (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
- PMC3142633
Electronic International Standard Serial Number (EISSN)
- 1937-335X
Digital Object Identifier (DOI)
- 10.1089/ten.TEA.2010.0631
Language
- eng
Conference Location
- United States