on December 31, 2001
Circulation. 2001
Published online before print December 31, 2001, doi: 10.1161/hc0602.103673
Published online before print December 31, 2001, doi: 10.1161/hc0602.103673
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Submitted on October 12, 2001
From the Division of Cardiovascular Research
and Medicine (H.I., J.Y., C.K., S.M., H.M., S.H., M.S., T.L., J.M.I.,
T.A.), St Elizabeth's Medical Center, Tufts University School of
Medicine, Boston, Mass; and the Department of Physiology (H.I.) and
Institute of Medical Science (T.A.), Tokai University School of
Medicine, Japan. * To whom correspondence should be addressed. E-mail: asa777{at}aol.com.
Background—Previous
studies have established that bone marrow--derived
endothelial progenitor cells (EPCs) are present in
the systemic circulation. In the current study, we investigated the
hypothesis that gene transfer can be used to achieve phenotypic
modulation of EPCs. Methods and Results—In
vitro, ex vivo murine vascular endothelial growth
factor (VEGF) 164 gene transfer augmented EPC proliferative activity
and enhanced adhesion and incorporation of EPCs into quiescent as well
as activated endothelial cell monolayers. To
determine if such phenotypic modulation may facilitate therapeutic
neovascularization, heterologous EPCs transduced with adenovirus
encoding VEGF were administered to athymic nude mice with hindlimb
ischemia; neovascularization and blood flow recovery were both
improved, and limb necrosis/autoamputation were reduced by 63.7% in
comparison with control animals. The dose of EPCs used for the in vivo
experiments was 30 times less than that required in previous trials of
EPC transplantation to improve ischemic limb salvage. Necropsy
analysis of animals that received DiI-labeled VEGF-transduced
EPCs confirmed that enhanced EPC incorporation demonstrated in vitro
contributed to in vivo neovascularization as
well. Conclusions—In vitro,
VEGF EPC gene transfer enhances EPC proliferation, adhesion, and
incorporation into endothelial cell monolayers. In
vivo, gene-modified EPCs facilitate the strategy of cell
transplantation to augment naturally impaired neovascularization in an
animal model of experimentally induced limb
ischemia.
Revised on November 29, 2001
Accepted on December 14, 2001
Endothelial Progenitor Cell
Vascular Endothelial Growth Factor Gene Transfer for
Vascular Regeneration
Key words: gene therapy • endothelium • angiogenesis • ischemia
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E. Ribourtout and J. Raymond Gene Therapy and Endovascular Treatment of Intracranial Aneurysms Stroke, March 1, 2004; 35(3): 786 - 793. [Abstract] [Full Text] [PDF]
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 K. M. Downs, E. R. Hellman, J. McHugh, K. Barrickman, and K. E. Inman Investigation into a role for the primitive streak in development of the murine allantois Development, January 1, 2004; 131(1): 37 - 55. [Abstract] [Full Text] [PDF]
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H.-J. Cho, H.-S. Kim, M.-M. Lee, D.-H. Kim, H.-J. Yang, J. Hur, K.-K. Hwang, S. Oh, Y.-J. Choi, I.-H. Chae, et al. Mobilized Endothelial Progenitor Cells by Granulocyte-Macrophage Colony-Stimulating Factor Accelerate Reendothelialization and Reduce Vascular Inflammation After Intravascular Radiation Circulation, December 9, 2003; 108(23): 2918 - 2925. [Abstract] [Full Text] [PDF]
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C. Herder, T. Tonn, R. Oostendorp, S. Becker, U. Keller, C. Peschel, M. Grez, and E. Seifried Sustained Expansion and Transgene Expression of Coagulation Factor VIII-Transduced Cord Blood-Derived Endothelial Progenitor Cells Arterioscler Thromb Vasc Biol, December 1, 2003; 23(12): 2266 - 2272. [Abstract] [Full Text] [PDF]
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P. E. Szmitko, C.-H. Wang, R. D. Weisel, G. A. Jeffries, T. J. Anderson, and S. Verma Biomarkers of Vascular Disease Linking Inflammation to Endothelial Activation: Part II Circulation, October 28, 2003; 108(17): 2041 - 2048. [Full Text] [PDF]
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B. R. Stoll, C. Migliorini, A. Kadambi, L. L. Munn, and R. K. Jain A mathematical model of the contribution of endothelial progenitor cells to angiogenesis in tumors: implications for antiangiogenic therapy Blood, October 1, 2003; 102(7): 2555 - 2561. [Abstract] [Full Text] [PDF]
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J. S. Forrester, M. J. Price, and R. R. Makkar Stem Cell Repair of Infarcted Myocardium: An Overview for Clinicians Circulation, September 2, 2003; 108(9): 1139 - 1145. [Full Text] [PDF]
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C. Heeschen, A. Aicher, R. Lehmann, S. Fichtlscherer, M. Vasa, C. Urbich, C. Mildner-Rihm, H. Martin, A. M. Zeiher, and S. Dimmeler Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization Blood, August 15, 2003; 102(4): 1340 - 1346. [Abstract] [Full Text] [PDF]
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T.-S. Li, K. Hamano, M. Nishida, M. Hayashi, H. Ito, A. Mikamo, and M. Matsuzaki CD117+ stem cells play a key role in therapeutic angiogenesis induced by bone marrow cell implantation Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H931 - H937. [Abstract] [Full Text] [PDF]
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M. Hristov, W. Erl, and P. C. Weber Endothelial Progenitor Cells: Mobilization, Differentiation, and Homing Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1185 - 1189. [Abstract] [Full Text] [PDF]
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C. Patterson The Ponzo Effect: Endothelial Progenitor Cells Appear on the Horizon Circulation, June 24, 2003; 107(24): 2995 - 2997. [Full Text] [PDF]
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P. E. Szmitko, P. W.M. Fedak, R. D. Weisel, D. J. Stewart, M. J.B. Kutryk, and S. Verma Endothelial Progenitor Cells: New Hope for a Broken Heart Circulation, June 24, 2003; 107(24): 3093 - 3100. [Full Text] [PDF]
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H. M. Nugent and E. R. Edelman Tissue Engineering Therapy for Cardiovascular Disease Circ. Res., May 30, 2003; 92(10): 1068 - 1078. [Abstract] [Full Text] [PDF]
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A. Luttun and P. Carmeliet De novo vasculogenesis in the heart Cardiovasc Res, May 1, 2003; 58(2): 378 - 389. [Abstract] [Full Text] [PDF]
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H. Masuda and T. Asahara Post-natal endothelial progenitor cells for neovascularization in tissue regeneration Cardiovasc Res, May 1, 2003; 58(2): 390 - 398. [Abstract] [Full Text] [PDF]
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T. Suzuki, M. Nishida, S. Futami, K. Fukino, T. Amaki, K. Aizawa, S. Chiba, H. Hirai, K. Maekawa, and R. Nagai Neoendothelialization after peripheral blood stem cell transplantation in humans: A case report of a Tokaimura nuclear accident victim Cardiovasc Res, May 1, 2003; 58(2): 487 - 492. [Abstract] [Full Text] [PDF]
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A. Aicher, W. Brenner, M. Zuhayra, C. Badorff, S. Massoudi, B. Assmus, T. Eckey, E. Henze, A. M. Zeiher, and S. Dimmeler Assessment of the Tissue Distribution of Transplanted Human Endothelial Progenitor Cells by Radioactive Labeling Circulation, April 29, 2003; 107(16): 2134 - 2139. [Abstract] [Full Text] [PDF]
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T. M. DOHERTY, P. K. SHAH, and T. B. RAJAVASHISTH Cellular origins of atherosclerosis: towards ontogenetic endgame? FASEB J, April 1, 2003; 17(6): 592 - 597. [Full Text] [PDF]
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J. Rehman, J. Li, C. M. Orschell, and K. L. March Peripheral Blood "Endothelial Progenitor Cells" Are Derived From Monocyte/Macrophages and Secrete Angiogenic Growth Factors Circulation, March 4, 2003; 107(8): 1164 - 1169. [Abstract] [Full Text] [PDF]
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E. C. Perin, Y.-J. Geng, and J. T. Willerson Adult Stem Cell Therapy in Perspective Circulation, February 25, 2003; 107(7): 935 - 938. [Full Text] [PDF]
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O. M. Tepper, R. D. Galiano, J. M. Capla, C. Kalka, P. J. Gagne, G. R. Jacobowitz, J. P. Levine, and G. C. Gurtner Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures Circulation, November 26, 2002; 106(22): 2781 - 2786. [Abstract] [Full Text] [PDF]
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 Y. Yang, J.-Y. Min, J. S. Rana, Q. Ke, J. Cai, Y. Chen, J. P. Morgan, and Y.-F. Xiao VEGF enhances functional improvement of postinfarcted hearts by transplantation of ESC-differentiated cells J Appl Physiol, September 1, 2002; 93(3): 1140 - 1151. [Abstract] [Full Text] [PDF]
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S. Murasawa, J. Llevadot, M. Silver, J. M. Isner, D. W. Losordo, and T. Asahara Constitutive Human Telomerase Reverse Transcriptase Expression Enhances Regenerative Properties of Endothelial Progenitor Cells Circulation, August 27, 2002; 106(9): 1133 - 1139. [Abstract] [Full Text] [PDF]
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E. G. Nabel Stem Cells Combined With Gene Transfer for Therapeutic Vasculogenesis: Magic Bullets? Circulation, February 12, 2002; 105(6): 672 - 674. [Full Text] [PDF]
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