Skeletal muscle cells expressing VEGF induce capillary formation and reduce cardiac injury in rats

We tested a preemptive combined cell/gene therapy strategy of skeletal myoblasts transfected with Ad 5RSVVEGF-165 in an ischemia/reperfusion rat model to increase collateral blood flow to nonischemic heart tissue. Lewis rats were injected with placebo (Control), 10 6 skeletal myoblasts (SkM), or 10 6 skeletal myoblasts transfected with Ad 5RSVVEGF-165 (SkM +) into the left ventricle 1 week before ischemia. Left ventricle end-diastolic pressure, scar area, and capillary density were assessed 4 weeks later. Local expression of human vascular endothelial growth factor was accompanied by an increase in capillary density in the SkM + group compared with that in the SkM and Control groups (700 ± 40 vs. 289 ± 18 and 318 ± 59 capillaries/mm 2, respectively; p < 0.05). After 3 weeks, the myocardial scar area was reduced in SkM + vs. Control (5.3 ± 0.4% and 14.8 ± 1.6%, p < 0.05), while injected cells alone (SkM) did not cause improvement compared with Control (11.8 ± 2.1% vs. 14.8 ± 1.6%, p > 0.05). The decrease in the scar area in SkM + was accompanied by an increase in the capillary density compared with that in SkM and Control 30 days after cell injection (1005 ± 108 vs. 524 ± 16 and 528 ± 26 capillaries/mm 2, respectively; p < 0.05). The scar areas were discrete (5.3–14.8%) and left ventricle end-diastolic pressure in all groups were comparable ( p > 0.05). The combined cell/gene therapy strategy of genetically modified myoblast cells expressing angiogenic factors injected into the myocardium induced capillary formation and prevented the extension and development of cardiac damage associated with ischemia/reperfusion in rats.