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

Abstract

Background: We tested a preemptive combined cell/gene therapy strategy of skeletal myoblasts transfected with Ad(5)RSVVEGF-165 in an ischemia/reperfusion rat model to increase collateral blood flow to nonischemic heart tissue.

Methods: Lewis rats were injected with placebo (Control), 10(6) skeletal myoblasts (SkM), or 10(6) skeletal myoblasts transfected with Ad(5)RSVVEGF-165 (SkM(+)) into the left ventricle 1week before ischemia. Left ventricle end-diastolic pressure, scar area, and capillary density were assessed 4weeks 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+/-59capillaries/mm(2), respectively; p<0.05). After 3weeks, 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 30days after cell injection (1005+/-108 vs. 524+/-16 and 528+/-26capillaries/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).

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.