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Increasing transplanted cell survival with cell-based angiogenic gene therapy
Terrence M Yau1, Christopher Kim, Dawn Ng
1Toronto 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
The Annals of Thoracic Surgery
|October 26, 2005
Summary
Cell transplantation for heart repair faces challenges with cell survival. Enhancing vascular endothelial growth factor (VEGF) improved cell survival by reducing apoptosis and ischemia, suggesting new strategies for myocardial repair.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Cell Biology
Background:
- Low survival rates of transplanted cells limit efficacy in myocardial repair.
- Apoptosis (programmed cell death) and ischemia contribute significantly to post-transplantation cell loss.
- Maximizing transplanted cell survival is crucial for successful cardiac regeneration.
Purpose of the Study:
- To investigate the role of apoptosis in cell loss following myocardial transplantation.
- To assess the impact of angiogenesis, induced by vascular endothelial growth factor (VEGF), on cell survival and apoptosis.
- To evaluate the efficacy of different cell types and VEGF transfection in promoting myocardial repair.
Main Methods:
- Myocardial cryoinjury was induced in female Lewis rats.
- Transplantation of heart cells, VEGF-transfected heart cells, skeletal myoblasts, or VEGF-transfected skeletal myoblasts.
- Quantification of transplanted cell survival and apoptosis using molecular assays (Y-chromosome DNA, TUNEL, DNA fragmentation).
Main Results:
- Approximately one-third of untransfected heart cells and skeletal myoblasts survived after 1 week.
- VEGF-transfected cells showed significantly higher survival rates (one-half) compared to untransfected cells (p < 0.05).
- Apoptosis was significantly reduced in VEGF-transfected groups, with the lowest levels observed in controls.
Conclusions:
- Both ischemia and apoptosis contribute to cell loss after transplantation into infarcted myocardium.
- VEGF-induced angiogenesis effectively reduced ischemic and apoptotic cell death, enhancing cell survival.
- Targeting apoptosis presents a promising strategy to improve the outcomes of cell transplantation for cardiac repair.