Arterial bypasses are frequently performed each year, which require autologous vessel or synthetic grafts to replace diseased arteries. Autologous vein grafts often have thin walls that are damaged after implantation and not all patients have suitable veins for grafting. Tissue engineering offers the potential to produce biological grafts for use in vascular bypass procedures. To date, the feasability of transplanted bioengineered blood vessels is limited by high thrombosis rates. Thrombomodulin (TM) is a potent anticoagulant/ anti-inflammatory glycoprotein that is densely expressed on the surface of quiescent endothelial cells (ECs). The expression of TM in cultured ECs is significantly reduced compared to native ECs. We therefore propose to augment the anticoagulant phenotype of cultured ECs by overexpressing TM via genetic engineering. The porcine TM gene will be cloned and incorporated into a retroviral vector for transfection into cultured porcine ECs. These genetically modified ECs will then be used to seed the luminal surface of an autologous porcine vessel. The effectiveness of the gene transfer and the anticoagulant function of these enhanced ECs will be further analyzed. Eventually, these bioengineered blood vessels will be tested in vivo to determine if TM overexpression translates to lower thrombosis rates.
| Poh, Melissa; Boyer, Matthew; Solan, Amy et al. (2005) Blood vessels engineered from human cells. Lancet 365:2122-4 |
