| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 23, 2001
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.
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,
This article has been cited by other articles:
![]() |
B. A. Mettler, V. L. Sales, C. L. Stucken, V. Anttila, K. Mendelson, J. Bischoff, and J. E. Mayer Jr Stem cell-derived, tissue-engineered pulmonary artery augmentation patches in vivo. Ann. Thorac. Surg., July 1, 2008; 86(1): 132 - 141. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. P.W. Rouhl, R. J. van Oostenbrugge, J. Damoiseaux, J.-W. C. Tervaert, and J. Lodder Endothelial Progenitor Cell Research in Stroke: A Potential Shift in Pathophysiological and Therapeutical Concepts Stroke, July 1, 2008; 39(7): 2158 - 2165. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Povsic and P. J. Goldschmidt-Clermont Review: Endothelial progenitor cells: markers of vascular reparative capacity Therapeutic Advances in Cardiovascular Disease, June 1, 2008; 2(3): 199 - 213. [Abstract] [PDF] |
||||
![]() |
A. Zampetaki, J. P. Kirton, and Q. Xu Vascular repair by endothelial progenitor cells Cardiovasc Res, June 1, 2008; 78(3): 413 - 421. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Kapadia, D. A. Popowich, and M. R. Kibbe Modified Prosthetic Vascular Conduits Circulation, April 8, 2008; 117(14): 1873 - 1882. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Yao, Z.-H. Liu, C. Zheng, X. Zhang, H. Chen, C. Zeng, and L.-S. Li Evaluation of renal vascular lesions using circulating endothelial cells in patients with lupus nephritis Rheumatology, April 1, 2008; 47(4): 432 - 436. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-H. Wang, W.-J. Cherng, N.-I Yang, C.-M. Hsu, C.-H. Yeh, Y.-J. Lan, J.-S. Wang, and S. Verma Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R811 - R818. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Suarez, B. R. Shepherd, D. A. Rao, and J. S. Pober Alloimmunity to Human Endothelial Cells Derived from Cord Blood Progenitors J. Immunol., December 1, 2007; 179(11): 7488 - 7496. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Wang, Y. Zheng, W. Zhang, H. Yu, K. Lou, Y. Zhang, Q. Qin, B. Zhao, Y. Yang, and R. Hui Polymorphisms of KDR Gene Are Associated With Coronary Heart Disease J. Am. Coll. Cardiol., August 21, 2007; 50(8): 760 - 767. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. K. Kissel, R. Lehmann, B. Assmus, A. Aicher, J. Honold, U. Fischer-Rasokat, C. Heeschen, I. Spyridopoulos, S. Dimmeler, and A. M. Zeiher Selective Functional Exhaustion of Hematopoietic Progenitor Cells in the Bone Marrow of Patients With Postinfarction Heart Failure J. Am. Coll. Cardiol., June 19, 2007; 49(24): 2341 - 2349. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Lamping Endothelial Progenitor Cells: Sowing the Seeds for Vascular Repair Circ. Res., May 11, 2007; 100(9): 1243 - 1245. [Full Text] [PDF] |
||||
![]() |
A. V. R. Santhanam, L. A. Smith, T. He, K. A. Nath, and Z. S. Katusic Endothelial Progenitor Cells Stimulate Cerebrovascular Production of Prostacyclin By Paracrine Activation of Cyclooxygenase-2 Circ. Res., May 11, 2007; 100(9): 1379 - 1388. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Murphy, G. S. Kanaganayagam, B. Jiang, P. J. Chowienczyk, R. Zbinden, M. Saha, S. Rahman, A. M. Shah, M. S. Marber, and M. T. Kearney Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 936 - 942. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. F. Luscher, J. Steffel, F. R. Eberli, M. Joner, G. Nakazawa, F. C. Tanner, and R. Virmani Drug-Eluting Stent and Coronary Thrombosis: Biological Mechanisms and Clinical Implications Circulation, February 27, 2007; 115(8): 1051 - 1058. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. V. Pislaru, A. Harbuzariu, R. Gulati, T. Witt, N. P. Sandhu, R. D. Simari, and G. S. Sandhu Magnetically Targeted Endothelial Cell Localization in Stented Vessels J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1839 - 1845. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. J. Capoccia, R. M. Shepherd, and D. C. Link G-CSF and AMD3100 mobilize monocytes into the blood that stimulate angiogenesis in vivo through a paracrine mechanism Blood, October 1, 2006; 108(7): 2438 - 2445. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Kiernan and R. D. Simari Vasculoprotective Effects of Erythropoietin: New Developments and New Alternatives Circ. Res., June 9, 2006; 98(11): 1341 - 1343. [Full Text] [PDF] |
||||
![]() |
N. Urao, M. Okigaki, H. Yamada, Y. Aadachi, K. Matsuno, A. Matsui, S. Matsunaga, K. Tateishi, T. Nomura, T. Takahashi, et al. Erythropoietin-Mobilized Endothelial Progenitors Enhance Reendothelialization via Akt-Endothelial Nitric Oxide Synthase Activation and Prevent Neointimal Hyperplasia Circ. Res., June 9, 2006; 98(11): 1405 - 1413. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Sata Role of Circulating Vascular Progenitors in Angiogenesis, Vascular Healing, and Pulmonary Hypertension: Lessons From Animal Models Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1008 - 1014. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Roy-Chaudhury, V. P. Sukhatme, and A. K. Cheung Hemodialysis Vascular Access Dysfunction: A Cellular and Molecular Viewpoint J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1112 - 1127. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Takamiya, M. Okigaki, D. Jin, S. Takai, Y. Nozawa, Y. Adachi, N. Urao, K. Tateishi, T. Nomura, K. Zen, et al. Granulocyte Colony-Stimulating Factor-Mobilized Circulating c-Kit+/Flk-1+ Progenitor Cells Regenerate Endothelium and Inhibit Neointimal Hyperplasia After Vascular Injury Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 751 - 757. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ii, H. Takenaka, J. Asai, K. Ibusuki, Y. Mizukami, K. Maruyama, Y.-s. Yoon, A. Wecker, C. Luedemann, E. Eaton, et al. Endothelial Progenitor Thrombospondin-1 Mediates Diabetes-Induced Delay in Reendothelialization Following Arterial Injury Circ. Res., March 17, 2006; 98(5): 697 - 704. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Langer, A. E. May, K. Daub, U. Heinzmann, P. Lang, M. Schumm, D. Vestweber, S. Massberg, T. Schonberger, I. Pfisterer, et al. Adherent Platelets Recruit and Induce Differentiation of Murine Embryonic Endothelial Progenitor Cells to Mature Endothelial Cells In Vitro Circ. Res., February 3, 2006; 98(2): e2 - e10. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. W. Liu, G. Pernod, S. Dunoyer-Geindre, R. J. Fish, H. Yang, H. Bounameaux, and E. K. O. Kruithof Promoter Dependence of Transgene Expression by Lentivirus-Transduced Human Blood-Derived Endothelial Progenitor Cells Stem Cells, January 1, 2006; 24(1): 199 - 208. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Doyle, N. Caplice, J. I. Rotmans, J. M.M. Heyligers, H. J.M. Verhagen, E. Velema, D. P.V. de Kleijn, G. Pasterkamp, M. M. Nagtegaal, E. S.G. Stroes, et al. Letter Regarding Article by Rotmans et al, "In Vivo Cell Seeding With Anti-CD34 Antibodies Successfully Accelerates Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenous Expanded Polytetrafluoroethylene Grafts" * Response Circulation, December 13, 2005; 112(24): e359 - e360. [Full Text] [PDF] |
||||
![]() |
I. Dimarakis, N. A. Habib, and M. Y.A. Gordon Adult bone marrow-derived stem cells and the injured heart: just the beginning? Eur. J. Cardiothorac. Surg., November 1, 2005; 28(5): 665 - 676. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Zhang, A. Zhang, D.E. Kohan, R.D. Nelson, F.J. Gonzales, T. Yang, C. Schmidt-Lucke, L. Rossig, S. Fichtlscherer, M. Vasa, et al. Edema and Congestive Heart Failure from Thiazolidone Insulin Sensitizers--Excess Sodium Reabsoption in the Collecting Duct: Collecting Duct-Specific Deletion of Peroxisome Proliferator-Activated Receptor {gamma} Blocks Thiazolidinedione-Induced Fluid Retention. Proc Nat Acad Sci U S A 102: 9406-9411, 2005 J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3139 - 3142. [Full Text] [PDF] |
||||
![]() |
R. Gulati and R. D. Simari Cell Therapy for Angiogenesis: Embracing Diversity Circulation, September 13, 2005; 112(11): 1522 - 1524. [Full Text] [PDF] |
||||
![]() |
P. Roy-Chaudhury Endothelial Progenitor Cells, Neointimal Hyperplasia, and Hemodialysis Vascular Access Dysfunction: Novel Therapies for a Recalcitrant Clinical Problem Circulation, July 5, 2005; 112(1): 3 - 5. [Full Text] [PDF] |
||||
![]() |
J. I. Rotmans, J. M.M. Heyligers, H. J.M. Verhagen, E. Velema, M. M. Nagtegaal, D. P.V. de Kleijn, F. G. de Groot, E. S.G. Stroes, and G. Pasterkamp In Vivo Cell Seeding With Anti-CD34 Antibodies Successfully Accelerates Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenous Expanded Polytetrafluoroethylene Grafts Circulation, July 5, 2005; 112(1): 12 - 18. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. J. Dzau, M. Gnecchi, A. S. Pachori, F. Morello, and L. G. Melo Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases Hypertension, July 1, 2005; 46(1): 7 - 18. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Schmidt-Lucke, L. Rossig, S. Fichtlscherer, M. Vasa, M. Britten, U. Kamper, S. Dimmeler, and A. M. Zeiher Reduced Number of Circulating Endothelial Progenitor Cells Predicts Future Cardiovascular Events: Proof of Concept for the Clinical Importance of Endogenous Vascular Repair Circulation, June 7, 2005; 111(22): 2981 - 2987. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Rossig, C. Urbich, T. Bruhl, E. Dernbach, C. Heeschen, E. Chavakis, K.-i. Sasaki, D. Aicher, F. Diehl, F. Seeger, et al. Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells J. Exp. Med., June 6, 2005; 201(11): 1825 - 1835. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Simons Angiogenesis: Where Do We Stand Now? Circulation, March 29, 2005; 111(12): 1556 - 1566. [Full Text] [PDF] |
||||
![]() |
T. He, T. E. Peterson, E. L. Holmuhamedov, A. Terzic, N. M. Caplice, L. W. Oberley, and Z. S. Katusic Human Endothelial Progenitor Cells Tolerate Oxidative Stress Due to Intrinsically High Expression of Manganese Superoxide Dismutase Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2021 - 2027. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Kong, L. G. Melo, M. Gnecchi, L. Zhang, G. Mostoslavsky, C. C. Liew, R. E. Pratt, and V. J. Dzau Cytokine-Induced Mobilization of Circulating Endothelial Progenitor Cells Enhances Repair of Injured Arteries Circulation, October 5, 2004; 110(14): 2039 - 2046. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
L. G. Melo, M. Gnecchi, A. S. Pachori, D. Kong, K. Wang, X. Liu, R. E. Pratt, and V. J. Dzau 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] |
||||
![]() |
T. He, L. A. Smith, S. Harrington, K. A. Nath, N. M. Caplice, and Z. S. Katusic Transplantation of Circulating Endothelial Progenitor Cells Restores Endothelial Function of Denuded Rabbit Carotid Arteries Stroke, October 1, 2004; 35(10): 2378 - 2384. [Abstract] [Full Text] [PDF] |
||||
![]() |
L.G Melo, M Gnecchi, A.S Pachori, K Wang, and V.J Dzau 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] |
||||
![]() |
C. Urbich and S. Dimmeler Endothelial Progenitor Cells: Characterization and Role in Vascular Biology Circ. Res., August 20, 2004; 95(4): 343 - 353. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Gulati, D. Jevremovic, T. A. Witt, L. S. Kleppe, R. G. Vile, A. Lerman, and R. D. Simari 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] |
||||
![]() |
D. Kong, L. G. Melo, A. A. Mangi, L. Zhang, M. Lopez-Ilasaca, M. A. Perrella, C. C. Liew, R. E. Pratt, and V. J. Dzau Enhanced Inhibition of Neointimal Hyperplasia by Genetically Engineered Endothelial Progenitor Cells Circulation, April 13, 2004; 109(14): 1769 - 1775. [Abstract] [Full Text] [PDF] |
||||
|
Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 2003 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |