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J Thorac Cardiovasc Surg 2001;122:963-971
© 2001 The American Association for Thoracic Surgery
Cardiopulmonary Support and Physiology (CSP) |
From the Division of Cardiovascular Surgery, Toronto General Hospital, Toronto General Research Institute, University Health Network, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
R.K.L. is a Career Investigator of the Heart and Stroke Foundation of Canada. R.D.W. was a Career Investigator of the Heart and Stroke Foundation of Ontario. This research was supported by research grants to R.K.L. from the Medical Research Council of Canada (MT-13665).
Received for publication Jan 17, 2001. Revisions requested May 8, 2001. Accepted for publication May 8, 2001. Address for reprints: Ren-Ke Li, MD, PhD, Department of Cardiovascular Surgery, Toronto General Hospital, CCRW 1-815, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4 (E-mail: RenKe{at}UHN.on.ca).
Abstract
Purpose: Myocardial angiogenesis may improve regional perfusion and perhaps function after cardiac injury. We evaluated the effect of endothelial cell transplantation into a myocardial scar on angiogenesis and ventricular function, as an alternative to angiogenic gene or protein therapy.
Methods and Results: A transmural myocardial scar was created in the left ventricular free wall of rat hearts by cryoinjury. Allogeneic aortic endothelial cells were injected into the scar 2 weeks after cryoinjury. A cluster of transplanted cells was identified at the site of injection 1 day and 1 week after transplantation, but not after 2 weeks. The size of this cluster of transplanted cells decreased as vascular density in the transplanted scar tissue increased with time. Six weeks after transplantation, vascular density was significantly greater in transplanted hearts than in control hearts. Regional blood flow, by microsphere analysis, was greater in the transplanted rats. Systolic and diastolic ventricular function was similar between groups. In a second series of experiments, syngeneic aortic endothelial cells labeled with bromodeoxyuridine were transplanted 2 weeks after cryoinjury. Vascular density in the transplanted scar was greater than in controls. Labeled transplanted endothelial cells were identified forming part of the newly developed blood vessels. No difference in vascular density was found between allogeneic and syngeneic cell transplantation. Vascular endothelial growth factor was not expressed at greater levels in the transplanted cells or the myocardial scar.
Conclusion: Transplanted endothelial cells stimulated angiogenesis, were incorporated into the new vessels, and increased regional perfusion in myocardial scar tissue, but did not improve global function in this cryoinjury rat model.
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J. Thorac. Cardiovasc. Surg. 2001 122: 851-852.
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