Ex vivo delivered stromal cell-derived factor-1α promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium

We aimed to optimize non-viral transfection of human stromal cell derived factor (SDF-1 alpha) gene into skeletal myoblasts (SkM) and, transplant these cells to establish transient SDF-1 alpha gradient to favor extra-cardiac stem cell translocation into infarcted heart. Optimized conditions for transfection of SDF-1 alpha gene into syngenic SkM were achieved using FuGene (TM) 6/phSDF-1 alpha (3:2v/w, 4 h transfection) with 125 mu M ZnCl2 (p < 0.001). After characterization for transgene overexpression by immunostaining, ELISA and PCR, the cells were transplanted in female rat model of myocardial infarction. Thirty-six rats were grouped (n = 12/group) to receive 70 mu l DMEM without cells (group-1) or containing 1.5 x 10(6) non-transfected (group-2) or SDF-1 alpha transfected SkM (group-3). On day 4 post-transplantation (in 4 animals/ group), marked expression of SDF-1 alpha/sry-gene (p=0.003), total Akt, phospho-Akt and Bcl2 was observed in group-3. The number of CD31(+), C-kit(+) and CD34(+) cells was highest in group-3 hearts (p < 0.01). Blood vessel density in group-3 was higher in both scar and peri-scar regions (p < 0.001) as compared with other groups. Echocardiography showed improved indices of left ventricle contractile function and remodeling in group-3 (p < 0.05) as compared with groups-1 and -2. We conclude that ex vivo SDF-1 alpha transgene delivery promotes stem and progenitor cell migration to the heart, activates cell survival signaling and enhances angiomyogenesis in the infarcted heart. (c) 2007 Elsevier Inc. All rights reserved.