Circulation. 2003;108:2710-2715
Published online before print November 3, 2003, doi: 10.1161/01.CIR.0000096490.16596.A6
Published online before print November 3, 2003, doi: 10.1161/01.CIR.0000096490.16596.A6
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(Circulation. 2003;108:2710.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Isolation and Transplantation of Autologous Circulating Endothelial Cells Into Denuded Vessels and Prosthetic Grafts
Implications for Cell-Based Vascular Therapy
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.).
Correspondence to Victor J. Dzau, MD, Department of Medicine, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail vdzau{at}partners.org
Received October 23, 2001; de novo received May 16, 2003; revision received July 24, 2003; accepted July 28, 2003.
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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