Effects of cell-based angiogenic gene therapy at 6 months: persistent angiogenesis and absence of oncogenicity.
BACKGROUND
Transplantation of vascular endothelial growth factor (VEGF)-transfected cells into myocardial scar enhances angiogenesis and may support the transplanted cells. We evaluated the effect of cell type, time, and location on the durability of this angiogenesis and potential oncogenicity.


METHODS
Lewis rats underwent myocardial cryoinjury 3 weeks before transplantation with heart cells (HC [a mixed culture of cardiomyocytes, smooth muscle cells, endothelial cells, and fibroblasts]), VEGF-transfected heart cells (HC+), skeletal myoblasts (Sk), VEGF-transfected skeletal myoblasts (Sk+), or medium (control) (n = 3 per group x 5 groups x 5 timepoints). Three days, 1 week, 2 weeks, 4 weeks, and 6 months after transplantation, hearts were excised and the scar, border zone, and normal myocardium evaluated for angioma or sarcoma formation, and vascular density quantitated.


RESULTS
Vascular densities were lowest in controls, intermediate in HC and Sk (p < 0.05) and highest in HC+ and Sk+ (p < 0.05). Densities were highest in the border zone, intermediate in normal myocardium, and lowest in the scar (p < 0.05), peaking in the border zone of HC+ and Sk+ hearts at 4 weeks. At 6 months, densities were greater in HC and Sk than controls (p < 0.05), and higher in Sk+ than Sk (p < 0.05), but HC+ and HC were similar. There was no evidence of angioma or sarcoma formation at any timepoint.


CONCLUSIONS
Angiogenesis induced by HC and Sk transplantation lasts at least 6 months and is increased by transfection with VEGF without apparent oncogenicity. The durability of the VEGF effect on vascular densities may be greater with Sk.
Kim
Christopher
C
Division of Cardiovascular Surgery, Toronto General Hospital, Toronto, Ontario, Canada.
Li
Ren-Ke
RK
Li
Guangming
G
Zhang
Yaoguang
Y
Weisel
Richard D
RD
Yau
Terrence M
TM
D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D002478:Cells, Cultured; D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D005615:Freezing; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006335:Heart Injuries / Q000209:etiology / Q000601:surgery*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology; D032446:Myoblasts / Q000378:metabolism* / Q000637:transplantation*; D009206:Myocardium / Q000166:cytology; D009369:Neoplasms / Q000209:etiology; D018919:Neovascularization, Physiologic / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A