Increasing transplanted cell survival with cell-based angiogenic gene therapy.
BACKGROUND
The majority of cells transplanted into infarcted myocardium do not survive. Maximizing cell survival should maximize the efficacy of cell transplantation for myocardial repair. We evaluated the role of apoptosis in cell loss after transplantation and the effect of angiogenesis on apoptosis and overall cell survival.


METHODS
Female Lewis rats underwent myocardial cryoinjury 3 weeks before transplantation with male heart cells (a mixed culture of cardiomyocytes, smooth muscle cells, endothelial cells, and fibroblasts), vascular endothelial growth factor-transfected heart cells, skeletal myoblasts, vascular endothelial growth factor-transfected skeletal myoblasts (n = 6 each), or medium (control, n = 5). One week later, transplanted cell survival and apoptosis were quantitated by real-time polymerase chain reaction for Y chromosomal deoxyribonucleic acid, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay and deoxyribonucleic acid fragmentation.


RESULTS
Approximately one third of heart cells and skeletal myoblasts survived 1 week after transplantation, and one half of vascular endothelial growth factor-transfected heart cells and skeletal myoblasts survived to this time (p < 0.05). Apoptosis was greatest in heart cell and skeletal myoblast-transplanted hearts (p < 0.05), reduced in the vascular endothelial growth factor-transfected groups (p < 0.05) and lowest in controls.


CONCLUSIONS
Ischemia and apoptosis both contribute to cell loss after transplantation. Transfection with vascular endothelial growth factor induced angiogenesis, which reduced both ischemic and apoptotic cell death. Our findings suggest that further strategies to reduce apoptosis may enhance the efficacy of cell transplantation in myocardial repair.
Yau
Terrence M
TM
Toronto General Hospital, University Health Network, Department of Surgery, University of Toronto, Heart and Stroke Foundation, Richard Lewar Centre of Excellence, Toronto, Ontario, Canada. terry.yau@utoronto.ca
Kim
Christopher
C
Ng
Dawn
D
Li
Guangming
G
Zhang
Yaoguang
Y
Weisel
Richard D
RD
Li
Ren-Ke
RK
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D015316:Genetic Therapy; D006329:Heart Conduction System; D006335:Heart Injuries / Q000628:therapy*; D032386:Myoblasts, Cardiac / Q000637:transplantation*; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D014998:Y Chromosome / Q000235:genetics*