| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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.
BackgroundPrevious
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 ResultsIn
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. ConclusionsIn 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
This article has been cited by other articles:
![]() |
M. S. Penn and A. A. Mangi Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy Circ. Res., June 20, 2008; 102(12): 1471 - 1482. [Abstract] [Full Text] [PDF] |
||||
![]() |
C Kalka and I. Baumgartner Gene and stem cell therapy in peripheral arterial occlusive disease Vascular Medicine, May 1, 2008; 13(2): 157 - 172. [Abstract] [PDF] |
||||
![]() |
T. Kinnaird, E. Stabile, S. Zbinden, M.-S. Burnett, and S. E. Epstein Cardiovascular risk factors impair native collateral development and may impair efficacy of therapeutic interventions Cardiovasc Res, May 1, 2008; 78(2): 257 - 264. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. C. Rafii, B. Psaila, J. Butler, D. K. Jin, and D. Lyden Regulation of Vasculogenesis by Platelet-Mediated Recruitment of Bone Marrow-Derived Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 217 - 222. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Dulak, J. Deshane, A. Jozkowicz, and A. Agarwal Heme Oxygenase-1 and Carbon Monoxide in Vascular Pathobiology: Focus on Angiogenesis Circulation, January 15, 2008; 117(2): 231 - 241. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Pi and C. Patterson Twin Layers of Lightning: A New Role for the Chaperone Hsp90 in Angiogenesis Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 6 - 7. [Full Text] [PDF] |
||||
![]() |
Z. Pasha, Y. Wang, R. Sheikh, D. Zhang, T. Zhao, and M. Ashraf Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium Cardiovasc Res, January 1, 2008; 77(1): 134 - 142. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Tongers and D. W. Losordo Frontiers in Nephrology: The Evolving Therapeutic Applications of Endothelial Progenitor Cells J. Am. Soc. Nephrol., November 1, 2007; 18(11): 2843 - 2852. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Xu, A. Mora, H. Shim, A. Stecenko, K. L. Brigham, and M. Rojas Role of the SDF-1/CXCR4 Axis in the Pathogenesis of Lung Injury and Fibrosis Am. J. Respir. Cell Mol. Biol., September 1, 2007; 37(3): 291 - 299. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Shmilovich, V. Deutsch, A. Roth, H. Miller, G. Keren, and J. George Circulating endothelial progenitor cells in patients with cardiac syndrome X Heart, September 1, 2007; 93(9): 1071 - 1076. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Xin, M. Kanehira, H. Mizuguchi, T. Hayakawa, T. Kikuchi, T. Nukiwa, and Y. Saijo Targeted Delivery of CX3CL1 to Multiple Lung Tumors by Mesenchymal Stem Cells Stem Cells, July 1, 2007; 25(7): 1618 - 1626. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Kubo, T.-S. Li, R. Suzuki, M. Ohshima, S.-L. Qin, and K. Hamano Short-term pretreatment with low-dose hydrogen peroxide enhances the efficacy of bone marrow cells for therapeutic angiogenesis Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2582 - H2588. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. L.T. Ballard and J. M. Edelberg Stem Cells and the Regeneration of the Aging Cardiovascular System Circ. Res., April 27, 2007; 100(8): 1116 - 1127. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Heeschen, E. Chang, A. Aicher, and J. P. Cooke Endothelial Progenitor Cells Participate in Nicotine-Mediated Angiogenesis J. Am. Coll. Cardiol., November 28, 2006; (2006) j.jacc.2006.07.066v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Fujii, S.-H. Li, P. E. Szmitko, P. W.M. Fedak, and S. Verma C-Reactive Protein Alters Antioxidant Defenses and Promotes Apoptosis in Endothelial Progenitor Cells Arterioscler. Thromb. Vasc. Biol., November 1, 2006; 26(11): 2476 - 2482. [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. Ishikawa, M. Eguchi, M. Wada, Y. Iwami, K. Tono, H. Iwaguro, H. Masuda, T. Tamaki, and T. Asahara Establishment of a Functionally Active Collagen-Binding Vascular Endothelial Growth Factor Fusion Protein In Situ Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 1998 - 2004. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.-P. Lee, S.-W. Youn, H.-J. Cho, L. Li, T.-Y. Kim, H.-S. Yook, J.-W. Chung, J. Hur, C.-H. Yoon, K.-W. Park, et al. Integrin-Linked Kinase, a Hypoxia-Responsive Molecule, Controls Postnatal Vasculogenesis by Recruitment of Endothelial Progenitor Cells to Ischemic Tissue Circulation, July 11, 2006; 114(2): 150 - 159. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Zentilin, S. Tafuro, S. Zacchigna, N. Arsic, L. Pattarini, M. Sinigaglia, and M. Giacca Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels Blood, May 1, 2006; 107(9): 3546 - 3554. [Abstract] [Full Text] [PDF] |
||||
![]() |
S Enomoto, M Yoshiyama, T Omura, R Matsumoto, T Kusuyama, D Nishiya, Y Izumi, K Akioka, H Iwao, K Takeuchi, et al. Microbubble destruction with ultrasound augments neovascularisation by bone marrow cell transplantation in rat hind limb ischaemia Heart, April 1, 2006; 92(4): 515 - 520. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. E.J. Reinders, T. J. Rabelink, and D. M. Briscoe Angiogenesis and Endothelial Cell Repair in Renal Disease and Allograft Rejection J. Am. Soc. Nephrol., April 1, 2006; 17(4): 932 - 942. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Rafii and D. Lyden Contribution of Hematopoietic and Vascular Progenitor Cells to the Neoangiogenic Niche Am. Assoc. Cancer Res. Educ. Book, April 1, 2006; 2006(1): 181 - 185. [Full Text] [PDF] |
||||
![]() |
F. G.P. Welt and D. W. Losordo Cell Therapy for Acute Myocardial Infarction: Curb Your Enthusiasm? Circulation, March 14, 2006; 113(10): 1272 - 1274. [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] |
||||
![]() |
A. N. Patel, L. Geffner, R. F. Vina, J. Saslavsky, H. C. Urschel Jr, R. Kormos, and F. Benetti Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: A prospective randomized study J. Thorac. Cardiovasc. Surg., December 1, 2005; 130(6): 1631 - 1638. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Landazuri and W. R. Taylor The stem cell shell game. Focus on "The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture" Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1361 - C1362. [Full Text] [PDF] |
||||
![]() |
D. M. Smadja, I. Bieche, G. Uzan, H. Bompais, L. Muller, C. Boisson-Vidal, M. Vidaud, M. Aiach, and P. Gaussem PAR-1 Activation on Human Late Endothelial Progenitor Cells Enhances Angiogenesis In Vitro With Upregulation of the SDF-1/CXCR4 System Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2321 - 2327. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Nishiyama, K. Takaji, K. Kataoka, Y. Kurihara, M. Yoshimura, A. Kato, H. Ogawa, and H. Kurihara Id1 Gene Transfer Confers Angiogenic Property on Fully Differentiated Endothelial Cells and Contributes to Therapeutic Angiogenesis Circulation, November 1, 2005; 112(18): 2840 - 2850. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Lenk, V. Adams, P. Lurz, S. Erbs, A. Linke, S. Gielen, A. Schmidt, D. Scheinert, G. Biamino, F. Emmrich, et al. Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia Eur. Heart J., September 2, 2005; 26(18): 1903 - 1909. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Wang, G. M. Riha, S. Yan, M. Li, H. Chai, H. Yang, Q. Yao, and C. Chen Shear Stress Induces Endothelial Differentiation From a Murine Embryonic Mesenchymal Progenitor Cell Line Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1817 - 1823. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Siepe, C. Heilmann, P. von Samson, P. Menasche, and F. Beyersdorf Stem cell research and cell transplantation for myocardial regeneration Eur. J. Cardiothorac. Surg., August 1, 2005; 28(2): 318 - 324. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Kucia, R. Reca, K. Miekus, J. Wanzeck, W. Wojakowski, A. Janowska-Wieczorek, J. Ratajczak, and M. Z. Ratajczak Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells Involve Similar Mechanisms: Pivotal Role of the SDF-1-CXCR4 Axis Stem Cells, August 1, 2005; 23(7): 879 - 894. [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] |
||||
![]() |
H.-J. Cho, S.-W. Youn, S.-I. Cheon, T.-Y. Kim, J. Hur, S.-Y. Zhang, S. P. Lee, K.-W. Park, M.-M. Lee, Y.-S. Choi, et al. Regulation of Endothelial Cell and Endothelial Progenitor Cell Survival and Vasculogenesis by Integrin-Linked Kinase Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1154 - 1160. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Costa and D. I. Simon Molecular Basis of Restenosis and Drug-Eluting Stents Circulation, May 3, 2005; 111(17): 2257 - 2273. [Full Text] [PDF] |
||||
![]() |
P. L Weissberg and A. Qasim Stem cell therapy for myocardial repair Heart, May 1, 2005; 91(5): 696 - 702. [Full Text] [PDF] |
||||
![]() |
S. Murasawa and T. Asahara Endothelial Progenitor Cells for Vasculogenesis Physiology, February 1, 2005; 20(1): 36 - 42. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. S. Goligorsky Whispers and shouts in the pathogenesis of acute renal ischaemia Nephrol. Dial. Transplant., February 1, 2005; 20(2): 261 - 266. [Full Text] [PDF] |
||||
![]() |
O. M. Tepper, J. M. Capla, R. D. Galiano, D. J. Ceradini, M. J. Callaghan, M. E. Kleinman, and G. C. Gurtner Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells Blood, February 1, 2005; 105(3): 1068 - 1077. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Iwase, N. Nagaya, T. Fujii, T. Itoh, H. Ishibashi-Ueda, M. Yamagishi, K. Miyatake, T. Matsumoto, S. Kitamura, and K. Kangawa Adrenomedullin Enhances Angiogenic Potency of Bone Marrow Transplantation in a Rat Model of Hindlimb Ischemia Circulation, January 25, 2005; 111(3): 356 - 362. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Grisar, D. Aletaha, C. W. Steiner, T. Kapral, S. Steiner, D. Seidinger, G. Weigel, I. Schwarzinger, W. Wolozcszuk, G. Steiner, et al. Depletion of Endothelial Progenitor Cells in the Peripheral Blood of Patients With Rheumatoid Arthritis Circulation, January 18, 2005; 111(2): 204 - 211. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Schuh, S. Breuer, R. Al Dashti, N. Sulemanjee, P. Hanrath, C. Weber, B. F. Uretsky, and E. R. Schwarz Administration of Vascular Endothelial Growth Factor Adjunctive to Fetal Cardiomyocyte Transplantation and Improvement of Cardiac Function in the Rat Model Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2005; 10(1): 55 - 66. [Abstract] [PDF] |
||||
![]() |
A. Hoeben, B. Landuyt, M. S. Highley, H. Wildiers, A. T. Van Oosterom, and E. A. De Bruijn Vascular Endothelial Growth Factor and Angiogenesis Pharmacol. Rev., December 1, 2004; 56(4): 549 - 580. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Bieberich, J. Silva, G. Wang, K. Krishnamurthy, and B. G. Condie Selective apoptosis of pluripotent mouse and human stem cells by novel ceramide analogues prevents teratoma formation and enriches for neural precursors in ES cell-derived neural transplants J. Cell Biol., November 22, 2004; 167(4): 723 - 734. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-H. Choi, J. Hur, C.-H. Yoon, J.-H. Kim, C.-S. Lee, S.-W. Youn, I.-Y. Oh, C. Skurk, T. Murohara, Y.-B. Park, et al. Augmentation of Therapeutic Angiogenesis Using Genetically Modified Human Endothelial Progenitor Cells with Altered Glycogen Synthase Kinase-3{beta} Activity J. Biol. Chem., November 19, 2004; 279(47): 49430 - 49438. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Weber, A. Schober, and A. Zernecke Chemokines: Key Regulators of Mononuclear Cell Recruitment in Atherosclerotic Vascular Disease Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 1997 - 2008. [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] |
||||
![]() |
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. Asahara and A. Kawamoto Endothelial progenitor cells for postnatal vasculogenesis Am J Physiol Cell Physiol, September 1, 2004; 287(3): C572 - C579. [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] |
||||
![]() |
T. Kinnaird, E. Stabile, M. S. Burnett, and S. E. Epstein Bone Marrow-Derived Cells for Enhancing Collateral Development: Mechanisms, Animal Data, and Initial Clinical Experiences Circ. Res., August 20, 2004; 95(4): 354 - 363. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Yamaoka-Tojo, M. Ushio-Fukai, L. Hilenski, S. I. Dikalov, Y. E. Chen, T. Tojo, T. Fukai, M. Fujimoto, N. A. Patrushev, N. Wang, et al. IQGAP1, a Novel Vascular Endothelial Growth Factor Receptor Binding Protein, Is Involved in Reactive Oxygen Species--Dependent Endothelial Migration and Proliferation Circ. Res., August 6, 2004; 95(3): 276 - 283. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Hattan, D. Warltier, W. Gu, C. Kolz, W. M. Chilian, and D. Weihrauch Autologous vascular smooth muscle cell-based myocardial gene therapy to induce coronary collateral growth Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H488 - H493. [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. W. Losordo and S. Dimmeler Therapeutic Angiogenesis and Vasculogenesis for Ischemic Disease: Part II: Cell-Based Therapies Circulation, June 8, 2004; 109(22): 2692 - 2697. [Full Text] [PDF] |
||||
![]() |
J. Raymond, F. Guilbert, A. Metcalfe, G. Gevry, I. Salazkin, and O. Robledo Role of the Endothelial Lining in Recurrences After Coil Embolization: Prevention of Recanalization by Endothelial Denudation Stroke, June 1, 2004; 35(6): 1471 - 1475. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.-i. Hiasa, M. Ishibashi, K. Ohtani, S. Inoue, Q. Zhao, S. Kitamoto, M. Sata, T. Ichiki, A. Takeshita, and K. Egashira Gene Transfer of Stromal Cell-Derived Factor-1{alpha} Enhances Ischemic Vasculogenesis and Angiogenesis via Vascular Endothelial Growth Factor/Endothelial Nitric Oxide Synthase-Related Pathway: Next-Generation Chemokine Therapy for Therapeutic Neovascularization Circulation, May 25, 2004; 109(20): 2454 - 2461. [Abstract] |