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Ann Thorac Surg 2007;83:640-646
© 2007 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Effects of Cell-Based Angiogenic Gene Therapy at 6 Months: Persistent Angiogenesis and Absence of Oncogenicity

Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network, Department of Surgery, University of Toronto, and Heart and Stroke Foundation/Richard Lewar Centre of Excellence, Toronto, Ontario, Canada

Accepted for publication September 12, 2006.

^_* Address correspondence to Dr Yau, Division of Cardiovascular Surgery, Toronto General Hospital, 4N-470, 200 Elizabeth St, Toronto, ON M5G 2C4, Canada. (Email: terry.yau{at}uhn.on.ca).

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.

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Invited commentary

Bonaros Nikolaos, Rauf Rauend, and Kocher Alfred
Ann. Thorac. Surg. 2007 83: 646-647. [Extract] [Full Text] [PDF]

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