Combination of chemokine and angiogenic factor genes and mesenchymal stem cells could enhance angiogenesis and improve cardiac function after acute myocardial infarction in rats

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Abstract
Gene and stem-cell therapies hold promise for the treatment of ischemic cardiovascular disease. Combined stem cell, chemokine, and angiogenic growth factor gene therapy could augment angiogenesis, and better improve heart function in the infarcted myocardium. In order to prove this action, we established the animal model of myocardial infarction (MI) was by occlusion of the left anterior descending artery in rats. Seven days after surgery, 5.0 × 106 Ad-EGFP–MSC, 5.0 × 106 Ad-SDF-1–MSC, 5.0 × 106 Ad-VEGF–MSC, or 5.0 × 106 Ad-SDF–VEGF–MSC (Ad-SDF-1–VEGF–MSC) suspension in 0.2 ml of serum-free medium was injected into four sites in the infarcted hearts. Results showed that MSCs transfected with Ad-VEGF and Ad-SDF-1 produced more SDF-1 and VEGF protein than MSCs alone, the increased protein levels of VEGF and SDF-1 activated Akt in MSCs transfected with Ad-VEGF and Ad-SDF-1, and improved the survival capability of the MSCs in vitro and in vivo. These transplanted cells showed that the characteristic phenotype of cardiomyocyte (e.g., cTnt) and endothelial cells (e.g., CD31). Four weeks after transplantation, reduced infarct size and fibrosis, greater vascular density, and a thicker left ventricle wall were observed in Ad-SDF–VEGF–MSC group. Measurement of hemodynamic parameters showed an improvement in left ventricular performance in Ad-SDF–VEGF–MSC group compared with other groups. These results demonstrated that combination of chemokine and angiogenic factor gene and stem cells could enhance angiogenesis and improves cardiac function after acute myocardial infarction in rats.