923. Muscle Stem Cells Genetically Modified to

2 downloads 0 Views 87KB Size Report
MDSCs retrovirally transduced with nLacZ gene (MDSC-nLacZ) were used as control. Because the long-term unregulated VEGF expression has been shown to ...
CARDIOVASCULAR: MYOCARDINAL GENE THERAPY We induced HIF overexpression by transduction of cardiac myocytes with a HIF-1 alpha encoding adenovirus and VEGF overexpression by transduction of these cells with an adenovirus encoding a ZFP which acts as a transcriptional activator of VEGFA. We incubated cultured endothelial cells with conditioned medium from these myocytes and tested for changes in adhesion molecule expression compared to controls (beta-galactosidase transduced). We also used conditioned medium to assess the effect of HIF or ZFP-induced VEGF expression on stem cell adhesion to endothelial monolayers and stem cell chemotaxis. There was a significant increase in platelet endothelial cell adhesion molecule (PECAM)-1 (P = 0.011) and E-selectin (P = 0.04) expression and a decrease vascular cell adhesion molecule (VCAM)1 expression (P = 0.03) in endothelial cells incubated with conditioned media from HIF-1 alpha overexpressing cardiac myocytes compared to controls. There was a significant increase in adhesion of stem cells to endothelial monolayers incubated with conditioned medium from cardiac myocytes overexpressing HIF-1 alpha and VEGF compared to controls (11.1 ± 0.4 vs. 8.5 ± 0.5 cells/hpf [P