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

Background We tested a preemptive combined cell/gene therapy strategy of skeletal myoblasts transfected with Ad5RSVVEGF-165 in an ischemia/reperfusion rat model to increase collateral blood flow to nonischemic heart tissue. Methods Lewis rats were injected with placebo (Control), 106 skeletal myoblasts (SkM), or 106 skeletal myoblasts transfected with Ad5RSVVEGF-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. Results 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/mm2, 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/mm2, 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). Conclusions 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.