title: 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.
authors: Heart Institute (InCor)-LIM-13, University of São Paulo Medical School, São Paulo, Brazil.
authors: Claudia
authors: C
authors: Becker
authors: Silvia
authors: S
authors: Lacchini
authors: Alysson Renato
authors: AR
authors: Muotri
authors: Gustavo José Justo
authors: GJ
authors: da Silva
authors: Jussara Bianchi
authors: JB
authors: Castelli
authors: Paula F
authors: PF
authors: Vassallo
authors: Carlos Frederico Martins
authors: CF
authors: Menck
authors: José Eduardo
authors: JE
authors: Krieger