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on November 3, 2003

Circulation. 2003
Published online before print November 3, 2003, doi: 10.1161/01.CIR.0000096490.16596.A6
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Submitted on October 23, 2001
Revised on July 24, 2003
Accepted on July 28, 2003

Isolation and Transplantation of Autologous Circulating Endothelial Cells Into Denuded Vessels and Prosthetic Grafts. Implications for Cell-Based Vascular Therapy

Daniel P. Griese MD, Afshin Ehsan MD, Luis G. Melo PhD, Deling Kong PhD, Lunan Zhang MD, Michael J. Mann MD, Richard E. Pratt PhD, Richard C. Mulligan PhD, and Victor J. Dzau MD*

From the Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School (D.P.G., A.E., L.G.M., D.K., L.Z., M.J.M., R.E.P., V.J.D.), and Department of Genetics, Children’s Hospital, Boston, Mass (D.P.G., R.C.M.); and the Department of Physiology, Queen’s University, Kingston, Ontario, Canada (L.G.M.).

* To whom correspondence should be addressed. E-mail: vdzau{at}partners.org.

Background--Blood-borne endothelial cells originating from adult bone marrow were reported previously. These cells have the properties of an endothelial progenitor cell (EPC) and can be mobilized by cytokines and recruited to sites of neovascularization, where they differentiate into mature endothelial cells. Current protocols for isolation of EPCs from peripheral blood rely on enrichment and selection of CD34+ mononuclear cells.

Methods and Results--In this report, we describe a streamlined method for the isolation and expansion of EPCs from peripheral blood and evaluate their therapeutic potential for autologous cell-based therapy of injured blood vessels and prosthetic grafts. A subset of unfractionated mononuclear cells exhibited the potential to differentiate in vitro into endothelial cells under selective growth conditions. The cells were efficiently transduced ex vivo by a retroviral vector expressing the LacZ reporter gene and could be expanded to yield sufficient numbers for therapeutic applications. Transplantation of these cells into balloon-injured carotid arteries and into bioprosthetic grafts in rabbits led to rapid endothelialization of the denuded vessels and graft segments, resulting in significant reduction in neointima deposition.

Conclusions--We conclude that transplantation of EPCs may play a crucial role in reestablishing endothelial integrity in injured vessels, thereby inhibiting neointimal hyperplasia. These findings may have implications for novel and practical cell-based therapies for vascular disease.


Key words: cells • transplantation • grafting




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Home page
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[Abstract] [Full Text] [PDF]


Home page
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Circulation, October 5, 2004; 110(14): 2039 - 2046.
[Abstract] [Full Text] [PDF]


Home page
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M. Abedin, Y. Tintut, and L. L. Demer
Mesenchymal Stem Cells and the Artery Wall
Circ. Res., October 1, 2004; 95(7): 671 - 676.
[Abstract] [Full Text] [PDF]


Home page
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Endothelium-Targeted Gene and Cell-Based Therapies for Cardiovascular Disease
Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1761 - 1774.
[Abstract] [Full Text] [PDF]


Home page
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Stroke, October 1, 2004; 35(10): 2378 - 2384.
[Abstract] [Full Text] [PDF]


Home page
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Gene- and cell-based therapies for cardiovascular diseases: current status and future directions
Eur. Heart J. Suppl., September 1, 2004; 6(suppl_E): E24 - E35.
[Abstract] [Full Text]


Home page
Circ. Res.Home page
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Endothelial Progenitor Cells: Characterization and Role in Vascular Biology
Circ. Res., August 20, 2004; 95(4): 343 - 353.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
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Modulation of the vascular response to injury by autologous blood-derived outgrowth endothelial cells
Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H512 - H517.
[Abstract] [Full Text] [PDF]


Home page
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Enhanced Inhibition of Neointimal Hyperplasia by Genetically Engineered Endothelial Progenitor Cells
Circulation, April 13, 2004; 109(14): 1769 - 1775.
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