Circulation. 2002;106:2019-2025
Published online before print September 16, 2002, doi: 10.1161/01.CIR.0000031332.45480.79
Published online before print September 16, 2002, doi: 10.1161/01.CIR.0000031332.45480.79
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:2019.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Angiogenesis by Implantation of Peripheral Blood Mononuclear Cells and Platelets Into Ischemic Limbs
From the Department of Medicine II and Cardiovascular Center (O.I., H.M., S.F., K.A., Y.M., T.I.) and Radiology (H.K.), Kansai Medical University, Moriguchi, Osaka, Japan, and the Pharmacobioregulation Research Laboratory (Y.N.), Hanno Research Center, Hanno, Saitama, Japan.
Correspondence to Hiroaki Matsubara, MD, Department of Medicine II, Kansai Medical University, Moriguchi, Osaka 570-8507, Japan. E-mail matsubah{at}takii.kmu.ac.jp
Background— Peripheral blood mononuclear cells (PBMNCs), platelets, and polymorphonuclear leukocytes (PMNs) contain various angiogenic factors and cytokines.
Methods and Results— Unilateral hindlimb ischemia was surgically induced in athymic nude rats, and fluorescence-labeled human blood cells (PBMNCs [107 cells]+platelets [109] or PBMNCs [107]+platelets [109]+PMNs [107]) were intramuscularly implanted into the ischemic limbs. Laser Doppler imaging revealed markedly increased blood perfusion in PBMNC+platelet-implanted limbs (44% increase, P<0.001) compared with control implantation of human umbilical vein vascular endothelial cells. The addition of PMNs to PBMNCs+platelets attenuated blood perfusion (27% decrease, P<0.01). Neocapillary densities were increased by implantation of PBMNCs+platelets or platelets alone (3.5-fold and 2.4-fold, respectively; P<0.001), whereas PMNs inhibited (32%, P<0.05) PBMNC+ platelet-mediated capillary formation. There was no incorporation of implanted PBMNCs into neocapillaries, whereas PBMNCs and platelets accumulated around arterioles after implantation. Cellular extract from PBMNCs+platelets, in which vascular endothelial growth factor (VEGF), basic fibroblast growth factor, platelet-derived growth factor-AB, and transforming growth factor-ß were detected, markedly stimulated tubule formation of human umbilical vein vascular endothelial cells. Anti-VEGF neutralizing antibody markedly inhibited tubule formation and in vivo vessel formation. Neutrophil elastase inhibitor blocked the antiangiogenic action of PMNs, whereas inhibitors of oxygen metabolites had no effect.
Conclusions— This study demonstrated that implantation of PBMNCs and platelets into ischemic limbs effectively induces collateral vessel formation by supplying angiogenic factors (mainly VEGF) and cytokines, suggesting that this cell therapy is useful as a novel strategy for therapeutic angiogenesis.
Key Words: angiogenesis • vasculature • lymphocytes • blood cells • platelets
This article has been cited by other articles:
 |
|
 |
|
  R. Gulati and R. D. Simari Defining the potential for cell therapy for vascular disease using animal models Dis. Model. Mech., March 1, 2009; 2(3-4): 130 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Chappell, J. Song, A. L. Klibanov, and R. J. Price Ultrasonic Microbubble Destruction Stimulates Therapeutic Arteriogenesis Via the CD18-Dependent Recruitment of Bone Marrow-Derived Cells Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1117 - 1122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Urano, Y. Ito, M. Akao, T. Sawa, K. Miyata, M. Tabata, T. Morisada, T. Hato, M. Yano, T. Kadomatsu, et al. Angiopoietin-Related Growth Factor Enhances Blood Flow Via Activation of the ERK1/2-eNOS-NO Pathway in a Mouse Hind-Limb Ischemia Model Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 827 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Silvestre, Z. Mallat, A. Tedgui, and B. I. Levy Post-ischaemic neovascularization and inflammation Cardiovasc Res, May 1, 2008; 78(2): 242 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-W. Cho, S.-H. Moon, S.-H. Lee, S.-W. Kang, J. Kim, J. M. Lim, H.-S. Kim, B.-S. Kim, and H. M. Chung Improvement of Postnatal Neovascularization by Human Embryonic Stem Cell-Derived Endothelial-Like Cell Transplantation in a Mouse Model of Hindlimb Ischemia Circulation, November 20, 2007; 116(21): 2409 - 2419. [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]
|
|
|
|
 |
|
 S.-W. Cho, I.-K. Kim, S. H. Bhang, B. Joung, Y. J. Kim, K. J. Yoo, Y.-S. Yang, C. Y. Choi, and B.-S. Kim Combined therapy with human cord blood cell transplantation and basic fibroblast growth factor delivery for treatment of myocardial infarction Eur J Heart Fail, October 1, 2007; 9(10): 974 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tan, H. Shao, D. Eton, Z. Yang, L. Alonso-Diaz, H. Zhang, A. Schulick, A. S. Livingstone, and H. Yu Stromal cell-derived factor-1 enhances pro-angiogenic effect of granulocyte-colony stimulating factor Cardiovasc Res, March 1, 2007; 73(4): 823 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. I. Paraskevas, C. D. Liapis, D. D. Briana, and D. P. Mikhailidis Thromboangiitis Obliterans (Buerger's Disease): Searching for a Therapeutic Strategy Angiology, February 1, 2007; 58(1): 75 - 84. [Abstract] [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]
|
|
|
|
|
|
B. G. Sharifi, Z. Zeng, L. Wang, L. Song, H. Chen, M. Qin, M. R. Sierra-Honigmann, S. Wachsmann-Hogiu, and P. K. Shah Pleiotrophin Induces Transdifferentiation of Monocytes Into Functional Endothelial Cells Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1273 - 1280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lee, M. Aoki, T. Kondo, K. Kobayashi, K. Okumura, K. Komori, and T. Murohara Therapeutic Angiogenesis With Intramuscular Injection of Low-Dose Recombinant Granulocyte-Colony Stimulating Factor Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2535 - 2541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Imada, T. Tatsumi, Y. Mori, T. Nishiue, M. Yoshida, H. Masaki, M. Okigaki, H. Kojima, Y. Nozawa, Y. Nishiwaki, et al. Targeted Delivery of Bone Marrow Mononuclear Cells by Ultrasound Destruction of Microbubbles Induces Both Angiogenesis and Arteriogenesis Response Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2128 - 2134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Huang, S. Li, M. Han, Z. Xiao, R. Yang, and Z. C. Han Autologous Transplantation of Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells Improves Critical Limb Ischemia in Diabetes Diabetes Care, September 1, 2005; 28(9): 2155 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Izumi, S. Kim-Mitsuyama, M. Yoshiyama, T. Omura, M. Shiota, A. Matsuzawa, T. Yukimura, T. Murohara, M. Takeya, H. Ichijo, et al. Important Role of Apoptosis Signal-Regulating Kinase 1 in Ischemia-Induced Angiogenesis Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1877 - 1883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Amano, N. R. Hackett, S. Rafii, and R. G. Crystal Thrombopoietin Gene Transfer-Mediated Enhancement of Angiogenic Responses to Acute Ischemia Circ. Res., August 19, 2005; 97(4): 337 - 345. [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. Irie, T. Tatsumi, M. Takamiya, K. Zen, T. Takahashi, A. Azuma, K. Tateishi, T. Nomura, H. Hayashi, N. Nakajima, et al. Carbon Dioxide-Rich Water Bathing Enhances Collateral Blood Flow in Ischemic Hindlimb via Mobilization of Endothelial Progenitor Cells and Activation of NO-cGMP System Circulation, March 29, 2005; 111(12): 1523 - 1529. [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]
|
|
|
|
 |
|
 B. M. Prior, P. G. Lloyd, J. Ren, H. Li, H. T. Yang, M. H. Laughlin, and R. L. Terjung Time course of changes in collateral blood flow and isolated vessel size and gene expression after femoral artery occlusion in rats Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2434 - H2447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Song, P. S. Cottler, A. L. Klibanov, S. Kaul, and R. J. Price Microvascular remodeling and accelerated hyperemia blood flow restoration in arterially occluded skeletal muscle exposed to ultrasonic microbubble destruction Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2754 - H2761. [Abstract] [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]
|
|
|
|
|
|
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. 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]
|
|
|
|
|
|
A. Brill, H. Elinav, and D. Varon Differential role of platelet granular mediators in angiogenesis Cardiovasc Res, August 1, 2004; 63(2): 226 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Epstein, E. Stabile, T. Kinnaird, C. W. Lee, L. Clavijo, and M. S. Burnett Janus Phenomenon: The Interrelated Tradeoffs Inherent in Therapies Designed to Enhance Collateral Formation and Those Designed to Inhibit Atherogenesis Circulation, June 15, 2004; 109(23): 2826 - 2831. [Full Text] [PDF]
|
|
|
|
 |
|
 M.H. Tayebjee, G.Y.H. Lip, and R.J. MacFadyen Collateralization and the response to obstruction of epicardial coronary arteries QJM, May 1, 2004; 97(5): 259 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kinnaird, E. Stabile, M.S. Burnett, M. Shou, C.W. Lee, S. Barr, S. Fuchs, and S.E. Epstein Local Delivery of Marrow-Derived Stromal Cells Augments Collateral Perfusion Through Paracrine Mechanisms Circulation, March 30, 2004; 109(12): 1543 - 1549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kinnaird, E. Stabile, M.S. Burnett, C.W. Lee, S. Barr, S. Fuchs, and S.E. Epstein Marrow-Derived Stromal Cells Express Genes Encoding a Broad Spectrum of Arteriogenic Cytokines and Promote In Vitro and In Vivo Arteriogenesis Through Paracrine Mechanisms Circ. Res., March 19, 2004; 94(5): 678 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ziegelhoeffer, B. Fernandez, S. Kostin, M. Heil, R. Voswinckel, A. Helisch, and W. Schaper Bone Marrow-Derived Cells Do Not Incorporate Into the Adult Growing Vasculature Circ. Res., February 6, 2004; 94(2): 230 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fujiyama, K. Amano, K. Uehira, M. Yoshida, Y. Nishiwaki, Y. Nozawa, D. Jin, S. Takai, M. Miyazaki, K. Egashira, et al. Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1-Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells Circ. Res., November 14, 2003; 93(10): 980 - 989. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Jurasz, D. Alonso, S. Castro-Blanco, F. Murad, and M. W. Radomski Generation and role of angiostatin in human platelets Blood, November 1, 2003; 102(9): 3217 - 3223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bel, E. Messas, O. Agbulut, P. Richard, J. L. Samuel, P. Bruneval, A. A. Hagege, and P. Menasche Transplantation of Autologous Fresh Bone Marrow Into Infarcted Myocardium: A Word of Caution Circulation, September 9, 2003; 108(90101): II-247 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Chhokar and A. L. Tucker Angiogenesis: Basic Mechanisms and Clinical Applications Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 253 - 280. [Abstract] [PDF]
|
|