Gene therapy for myocardial angiogenesis: with direct intramuscular gene transfer of naked deoxyribonucleic acid encoding vascular endothelial growth factor and cell transplantation of vascular endothelial growth factor transfected H9c2 myoblast.
OBJECTIVE
We studied the therapeutic potential of ex vivo vascular endothelial growth factor (VEGF) gene-transduced H9c2 cell transplantation for myocardial neovascularization.


METHODS
The left ventricular free wall of adult Sprague-Dawley rats was cryodamaged. Two weeks after, naked plasmid encoding VEGF (VEGF1: 1 1microg/100 microl, VEGF5: 5 microg/100 microl), or VEGF transfected H9c2 myoblasts (0.5 x 10(6) cells/200 microl) were injected into the center of scar tissue. Four weeks after cryoinjury, scar diameters in the each group were measured. Neovascularization in the scar tissue was then quantified histologically.


RESULTS
Average scar tissue diameter 4 weeks after cryoinjury was as follows: TE (controls): 6.77 +/- 0.31 mm, H9c2: 5.08 +/- 0.43 mm; VEGF1: 5.90 +/- 0.20 mm; VEGF5: 4.50 +/- 0.24 mm. Scar tissue diameter was smaller in the 3 groups than in the control group (p < 0.05). Capillary density by histological examination increased in naked plasmid injection groups (VEGF1: 1,209.9 +/- 305.3/mm2; VEGF5: 1,072.0 +/- 230.8/mm2) versus controls (708.2 +/- 144.9/mm2, p < 0.05, p < 0.05), and H9c2 cell transplantation group (1,379.4 +/- 391.6/mm2) versus controls (p < 0.05).


CONCLUSIONS
VEGF-transfected H9c2 myoblasts can be implanted and survive in infarcted myocardium. The ability to develop angiogenesis in the H9c2 cell transplantation group was markedly similar to direct myocardial injection in naked plasmid encoding VEGF groups.
Sugimoto
Tsutomu
T
Second Department of Surgery, Yamagata University School of Medicine, Iida-nishi, Yamagata, Japan.
Inui
Kiyoshige
K
Shimazaki
Yasuhisa
Y
D000818:Animals; D017690:Cell Transplantation; D016228:Endothelial Growth Factors / Q000235:genetics / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000627:therapeutic use*; D008222:Lymphokines / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D032446:Myoblasts; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009204:Myocardial Revascularization; D018919:Neovascularization, Physiologic; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors