Circulation Research. 2005;97:314-322
Published online before print July 14, 2005, doi: 10.1161/01.RES.0000177670.72216.9b
Published online before print July 14, 2005, doi: 10.1161/01.RES.0000177670.72216.9b
© 2005 American Heart Association, Inc.
Molecular Medicine |
CD14+CD34low Cells With Stem Cell Phenotypic and Functional Features Are the Major Source of Circulating Endothelial Progenitors
From the Center for Research (P.R., F.A., F.L., E.L., B.M., F.F., L.C., L.M., L.L., S.D., F.M., G.G., E.M., S.R.), Transfer and High Education DENOTHE, University of Florence, Italy; the Deutches Rheuma Forschungszentrum (A.S., M.K.), Berlin, Germany; and the Department of Molecular Cardiology (S.D.), University of Frankfurt, Germany.
Correspondence to Sergio Romagnani, Dipartimento di Medicina Interna, Università di Firenze, Viale Morgagni 85 Firenze 50134-Italy. E-mail s.romagnani{at}dmi.unifi.it
Endothelial progenitor cells (EPCs) seem to be a promising tool for cell therapy of acute myocardial infarction, but their nature is still unclear. We show here that EPCs obtainable from peripheral blood (PB) derive from the adhesion-related selection in culture of a subset of CD14+ cells, which, when assessed by the highly-sensitive antibody-conjugated magnetofluorescent liposomes (ACMFL) technique, were found to express CD34. These CD14+CD34low cells represented a variable proportion at individual level of CD14+ cells, ranging from 0.6% to 8.5% of all peripheral-blood leukocytes, and constituted the dominant population among circulating KDR+ cells. By using the ACMFL technique, virtually all CD14+ cells present in the bone marrow were found to be CD14+CD34low double-positive cells. EPCs, as well as purified circulating CD14+CD34low cells, exhibited high expression of embryonic stem cell (SC) markers Nanog and Oct-4, which were downregulated in a STAT3-independent manner when they differentiated into endothelial cells (ECs). Moreover, circulating CD14+CD34low cells, but not CD14+CD34– cells, proliferated in response to SC growth factors, and exhibited clonogenicity and multipotency, as shown by their ability to differentiate not only into ECs, but also into osteoblasts, adipocytes, or neural cells. The results of this study may reconcile apparently contradictory data of the literature, showing the generation of PB-derived EPCs from either CD34+ or CD14+ cells. We suggest that the use of this previously unrecognized population of circulating CD14+CD34low cells, which exhibit both phenotypic and functional features of SCs, may be useful in improving cell-based therapies of vascular and tissue damage.
Key Words: endothelial progenitor cells • monocytes • CD14+CD34low cells • Nanog
This article has been cited by other articles:
 |
|
 |
|
  A. Gianella, U. Guerrini, M. Tilenni, L. Sironi, G. Milano, E. Nobili, S. Vaga, M. C. Capogrossi, E. Tremoli, and M. Pesce Magnetic resonance imaging of human endothelial progenitors reveals opposite effects on vascular and muscle regeneration into ischaemic tissues Cardiovasc Res, October 31, 2009; (2009) cvp325v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Shantsila and G. Y.H. Lip Monocyte Diversity in Myocardial Infarction. J. Am. Coll. Cardiol., July 7, 2009; 54(2): 139 - 142. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Krenning, P. Y. W. Dankers, J. W. Drouven, F. Waanders, C. F. M. Franssen, M. J. A. van Luyn, M. C. Harmsen, and E. R. Popa Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease Am J Physiol Renal Physiol, June 1, 2009; 296(6): F1314 - F1322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ronconi, C. Sagrinati, M. L. Angelotti, E. Lazzeri, B. Mazzinghi, L. Ballerini, E. Parente, F. Becherucci, M. Gacci, M. Carini, et al. Regeneration of Glomerular Podocytes by Human Renal Progenitors J. Am. Soc. Nephrol., February 1, 2009; 20(2): 322 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Li, A. Vincent, J. Cates, D. M. Brantley-Sieders, D. B. Polk, and P. P. Young Low Levels of Tumor Necrosis Factor {alpha} Increase Tumor Growth by Inducing an Endothelial Phenotype of Monocytes Recruited to the Tumor Site Cancer Res., January 1, 2009; 69(1): 338 - 348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Smadja, I. Bieche, J.-S. Silvestre, S. Germain, A. Cornet, I. Laurendeau, J.-P. Duong-Van-Huyen, J. Emmerich, M. Vidaud, M. Aiach, et al. Bone Morphogenetic Proteins 2 and 4 Are Selectively Expressed by Late Outgrowth Endothelial Progenitor Cells and Promote Neoangiogenesis Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2137 - 2143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Capoccia, A. D. Gregory, and D. C. Link Recruitment of the inflammatory subset of monocytes to sites of ischemia induces angiogenesis in a monocyte chemoattractant protein-1-dependent fashion J. Leukoc. Biol., September 1, 2008; 84(3): 760 - 768. [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]
|
|
|
|
 |
|
 S. Mieno, R. T. Clements, M. Boodhwani, N. R. Sodha, B. Ramlawi, C. Bianchi, and F. W. Sellke Characteristics and Function of Cryopreserved Bone Marrow-Derived Endothelial Progenitor Cells Ann. Thorac. Surg., April 1, 2008; 85(4): 1361 - 1366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Mazzinghi, E. Ronconi, E. Lazzeri, C. Sagrinati, L. Ballerini, M. L. Angelotti, E. Parente, R. Mancina, G. S. Netti, F. Becherucci, et al. Essential but differential role for CXCR4 and CXCR7 in the therapeutic homingof human renal progenitor cells J. Exp. Med., February 18, 2008; 205(2): 479 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Shantsila, T. Watson, H.-F. Tse, and G. Y.H. Lip New insights on endothelial progenitor cell subpopulations and their angiogenic properties. J. Am. Coll. Cardiol., February 12, 2008; 51(6): 669 - 671. [Full Text] [PDF]
|
|
|
|
 |
|
 W Wojakowski, M Kucia, M Kazmierski, M Z Ratajczak, and M Tendera Circulating progenitor cells in stable coronary heart disease and acute coronary syndromes: relevant reparatory mechanism? Heart, January 1, 2008; 94(1): 27 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lazzeri, C. Crescioli, E. Ronconi, B. Mazzinghi, C. Sagrinati, G. S. Netti, M. L. Angelotti, E. Parente, L. Ballerini, L. Cosmi, et al. Regenerative Potential of Embryonic Renal Multipotent Progenitors in Acute Renal Failure J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3128 - 3138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Beltrami, D. Cesselli, N. Bergamin, P. Marcon, S. Rigo, E. Puppato, F. D'Aurizio, R. Verardo, S. Piazza, A. Pignatelli, et al. Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow) Blood, November 1, 2007; 110(9): 3438 - 3446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Annunziato, L. Cosmi, V. Santarlasci, L. Maggi, F. Liotta, B. Mazzinghi, E. Parente, L. Fili, S. Ferri, F. Frosali, et al. Phenotypic and functional features of human Th17 cells J. Exp. Med., August 6, 2007; 204(8): 1849 - 1861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Sorrentino, F. H. Bahlmann, C. Besler, M. Muller, S. Schulz, N. Kirchhoff, C. Doerries, T. Horvath, A. Limbourg, F. Limbourg, et al. Oxidant Stress Impairs In Vivo Reendothelialization Capacity of Endothelial Progenitor Cells From Patients With Type 2 Diabetes Mellitus: Restoration by the Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Rosiglitazone Circulation, July 10, 2007; 116(2): 163 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tanaka, T. Era, S.-i. Nishikawa, and S. Kawamata Forced expression of Nanog in hematopoietic stem cells results in a {gamma}{delta}T-cell disorder Blood, July 1, 2007; 110(1): 107 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lasagni, R. Grepin, B. Mazzinghi, E. Lazzeri, C. Meini, C. Sagrinati, F. Liotta, F. Frosali, E. Ronconi, N. Alain-Courtois, et al. PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion Blood, May 15, 2007; 109(10): 4127 - 4134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Thum, D. Fraccarollo, S. Thum, M. Schultheiss, A. Daiber, P. Wenzel, T. Munzel, G. Ertl, and J. Bauersachs Differential Effects of Organic Nitrates on Endothelial Progenitor Cells Are Determined by Oxidative Stress Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 748 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Casamassimi, M. L. Balestrieri, C. Fiorito, C. Schiano, C. Maione, R. Rossiello, V. Grimaldi, V. Del Giudice, C. Balestrieri, B. Farzati, et al. Comparison Between Total Endothelial Progenitor Cell Isolation Versus Enriched Cd133+ Culture J. Biochem., April 1, 2007; 141(4): 503 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hristov, A. Zernecke, K. Bidzhekov, E. A. Liehn, E. Shagdarsuren, A. Ludwig, and C. Weber Importance of CXC Chemokine Receptor 2 in the Homing of Human Peripheral Blood Endothelial Progenitor Cells to Sites of Arterial Injury Circ. Res., March 2, 2007; 100(4): 590 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Thum, D. Fraccarollo, M. Schultheiss, S. Froese, P. Galuppo, J. D. Widder, D. Tsikas, G. Ertl, and J. Bauersachs Endothelial Nitric Oxide Synthase Uncoupling Impairs Endothelial Progenitor Cell Mobilization and Function in Diabetes Diabetes, March 1, 2007; 56(3): 666 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Thum, S. Hoeber, S. Froese, I. Klink, D. O. Stichtenoth, P. Galuppo, M. Jakob, D. Tsikas, S. D. Anker, P. A. Poole-Wilson, et al. Age-Dependent Impairment of Endothelial Progenitor Cells Is Corrected by Growth Hormone Mediated Increase of Insulin-Like Growth Factor-1 Circ. Res., February 16, 2007; 100(3): 434 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Boos, G. Y.H. Lip, and A. D. Blann Circulating Endothelial Cells in Cardiovascular Disease J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1538 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sagrinati, G. S. Netti, B. Mazzinghi, E. Lazzeri, F. Liotta, F. Frosali, E. Ronconi, C. Meini, M. Gacci, R. Squecco, et al. Isolation and Characterization of Multipotent Progenitor Cells from the Bowman's Capsule of Adult Human Kidneys J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2443 - 2456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.J.M. Loomans, H. Wan, R. de Crom, R. van Haperen, H.C. de Boer, P.J.M. Leenen, H.A. Drexhage, T.J. Rabelink, A.J. van Zonneveld, and F.J.T. Staal Angiogenic Murine Endothelial Progenitor Cells Are Derived From a Myeloid Bone Marrow Fraction and Can Be Identified by Endothelial NO Synthase Expression Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1760 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.C. de Boer, C. Verseyden, L.H. Ulfman, J.J. Zwaginga, I. Bot, E.A. Biessen, T.J. Rabelink, and A.J. van Zonneveld Fibrin and Activated Platelets Cooperatively Guide Stem Cells to a Vascular Injury and Promote Differentiation Towards an Endothelial Cell Phenotype Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1653 - 1659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Sharpe III, A. A. Teleron, B. Li, J. Price, M. S. Sands, K. Alford, and P. P. Young The Origin and in Vivo Significance of Murine and Human Culture-Expanded Endothelial Progenitor Cells Am. J. Pathol., May 1, 2006; 168(5): 1710 - 1721. [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]
|
|
|
|
|
|
T. Thum, D. Fraccarollo, P. Galuppo, D. Tsikas, S. Frantz, G. Ertl, and J. Bauersachs Bone marrow molecular alterations after myocardial infarction: Impact on endothelial progenitor cells Cardiovasc Res, April 1, 2006; 70(1): 50 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Anghelina, P. Krishnan, L. Moldovan, and N. I. Moldovan Monocytes/Macrophages Cooperate with Progenitor Cells during Neovascularization and Tissue Repair: Conversion of Cell Columns into Fibrovascular Bundles Am. J. Pathol., February 1, 2006; 168(2): 529 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Leri and J. Kajstura Endothelial Progenitor Cells: Unexpected Disclosures Circ. Res., August 19, 2005; 97(4): 299 - 301. [Full Text] [PDF]
|
|