HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Terrence M. Yau Richard D. Weisel Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yau, T. M. Articles by Li, R.-K. Search for Related Content PubMed PubMed Citation Articles by Yau, T. M. Articles by Li, R.-K. Related Collections Molecular biology

Ann Thorac Surg 2005;80:1779-1786
© 2005 The Society of Thoracic Surgeons

---

Original article: Cardiovascular

Increasing Transplanted Cell Survival With Cell-Based Angiogenic Gene Therapy

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 April 21, 2005.

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

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.

This article has been cited by other articles:

				J. Terrovitis, K. F. Kwok, R. Lautamaki, J. M. Engles, A. S. Barth, E. Kizana, J. Miake, M. K. Leppo, J. Fox, J. Seidel, et al. Ectopic Expression of the Sodium-Iodide Symporter Enables Imaging of Transplanted Cardiac Stem Cells In Vivo by Single-Photon Emission Computed Tomography or Positron Emission Tomography J. Am. Coll. Cardiol., November 11, 2008; 52(20): 1652 - 1660. [Abstract] [Full Text] [PDF]

				P. Farahmand, T. Y.Y. Lai, R. D. Weisel, S. Fazel, T. Yau, P. Menasche, and R.-K. Li Skeletal Myoblasts Preserve Remote Matrix Architecture and Global Function When Implanted Early or Late After Coronary Ligation Into Infarcted or Remote Myocardium Circulation, September 30, 2008; 118(14_suppl_1): S130 - S137. [Abstract] [Full Text] [PDF]

				P. Menasche Towards the second generation of skeletal myoblasts? Cardiovasc Res, August 1, 2008; 79(3): 355 - 356. [Full Text] [PDF]

				D. Spiegelstein, C. Kim, Y. Zhang, G. Li, R. D. Weisel, R.-K. Li, and T. M. Yau Combined transmyocardial revascularization and cell-based angiogenic gene therapy increases transplanted cell survival Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3311 - H3316. [Abstract] [Full Text] [PDF]

				T. M. Yau, C. Kim, G. Li, Y. Zhang, S. Fazel, D. Spiegelstein, R. D. Weisel, and R.-K. Li Enhanced Angiogenesis With Multimodal Cell-Based Gene Therapy Ann. Thorac. Surg., March 1, 2007; 83(3): 1110 - 1119. [Abstract] [Full Text] [PDF]

				T. M. Yau, A. DeGasperis, and L. DeGasperis Reply Ann. Thorac. Surg., March 1, 2007; 83(3): 1234 - 1234. [Full Text] [PDF]

				L. Ye, H. Kh. Haider, C. Guo, and E. K.W. Sim Cell-Based VEGF Delivery Prevents Donor Cell Apoptosis After Transplantation Ann. Thorac. Surg., March 1, 2007; 83(3): 1233 - 1234. [Full Text] [PDF]

				C. Kim, R.-K. Li, G. Li, Y. Zhang, R. D. Weisel, and T. M. Yau Effects of Cell-Based Angiogenic Gene Therapy at 6 Months: Persistent Angiogenesis and Absence of Oncogenicity Ann. Thorac. Surg., February 1, 2007; 83(2): 640 - 646. [Abstract] [Full Text] [PDF]

				B. Nikolaos, R. Rauend, and K. Alfred Invited commentary Ann. Thorac. Surg., February 1, 2007; 83(2): 646 - 647. [Full Text] [PDF]

				P. Menasche, M. Desnos, and A. A. Hagege Myoblast transplantation during cardiac surgery Eur. Heart J. Suppl., December 1, 2006; 8(suppl_H): H52 - H56. [Abstract] [Full Text] [PDF]