The goal of this project is to engineer an arterial substitute that is lined with functionally active autogenous endothelial cells. The hypothesis is that autologous endothelial progenitor cells can be easily obtained from peripheral blood, differentiated in ,culture to mature endothelial cells, transduced to over-express vascular endothelial growth factor (VEGF) ex vivo with a retroviral construct, and used to line an expanded polytetrafluroethylene (ePTFE) graft. The transfection is 80-90% efficient, rate of endothelialization as well as function of the endothelial layer will be tested in in vitro static and flow models, as well as in vivo. A graft lined with endothelial cells will not only resist thrombus formation (which we will test) but the addition of VEGF will not only enhance graft endothelialization, but will induce neo-vascularization in distal sites that are not amenable to surgical bypass in an in vivo model of chronic hind limb ischemia.
| Mangi, Abeel A; Noiseux, Nicolas; Kong, Deling et al. (2003) Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 9:1195-201 |
