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Review

Working hypothesis to redefine endothelial progenitor cells

Leukemia volume 21, pages 1141–1149 (2007)Cite this article

Abstract

Since 1997, postnatal vasculogenesis has been purported to be an important mechanism for neoangiogenesis via bone marrow (BM)-derived circulating endothelial progenitor cells (EPCs). Based on this paradigm, EPCs have been extensively studied as biomarkers to assess severity of cardiovascular disease and as a cell-based therapy for several human cardiovascular disorders. In the majority of studies to date, EPCs were identified and enumerated by two primary methodologies; EPCs were obtained and quantified following in vitro cell culture, or EPCs were identified and enumerated by flow cytometry. Both methods have proven controversial. This review will attempt to outline the definition of EPCs from some of the most widely cited published reports in an effort to provide a framework for understanding subsequent studies in this rapidly evolving field. We will focus this review on studies that used cell culture techniques to define EPCs.

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References

  1. Florey HW, Greer SJ, Poole JC, Werthessen NT . The pseudointima lining fabric grafts of the aorta. Br J Exp Pathol 1961; 42: 236–246.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Mackenzie DC, Loewenthal J . Endothelial growth in nylon vascular grafts. Br J Surg 1960; 48: 212–217.

    CAS  PubMed  Google Scholar 

  3. Poole JC, Sabiston Jr DC, Florey HW, Allison PR . Growth of endothelium in arterial prosthetic grafts and following endarterectomy. Surg Forum 1962; 13: 225–227.

    CAS  PubMed  Google Scholar 

  4. Stump MM, Jordan Jr GL, Debakey ME, Halpert B . Endothelium grown from circulating blood on isolated intravascular Dacron hub. Am J Pathol 1963; 43: 361–367.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Gaynor E, Bouvier C, Spaet TH . Vascular lesions: possible pathogenetic basis of the generalized Shwartzman reaction. Science 1970; 170: 986–988.

    CAS  PubMed  Google Scholar 

  6. George F, Brisson C, Poncelet P, Laurent JC, Massot O, Arnoux D et al. Rapid isolation of human endothelial cells from whole blood using S-Endo1 monoclonal antibody coupled to immuno-magnetic beads: demonstration of endothelial injury after angioplasty. Thromb Haemost 1992; 67: 147–153.

    CAS  PubMed  Google Scholar 

  7. Mutin M, Canavy I, Blann A, Bory M, Sampol J, Dignat-George F . Direct evidence of endothelial injury in acute myocardial infarction and unstable angina by demonstration of circulating endothelial cells. Blood 1999; 93: 2951–2958.

    CAS  PubMed  Google Scholar 

  8. Makin AJ, Blann AD, Chung NA, Silverman SH, Lip GY . Assessment of endothelial damage in atherosclerotic vascular disease by quantification of circulating endothelial cells. Relationship with von Willebrand factor and tissue factor. Eur Heart J 2004; 25: 371–376.

    CAS  PubMed  Google Scholar 

  9. Woywodt A, Streiber F, de Groot K, Regelsberger H, Haller H, Haubitz M . Circulating endothelial cells as markers for ANCA-associated small-vessel vasculitis. Lancet 2003; 361: 206–210.

    CAS  PubMed  Google Scholar 

  10. Woywodt A, Scheer J, Hambach L, Buchholz S, Ganser A, Haller H et al. Circulating endothelial cells as a marker of endothelial damage in allogeneic hematopoietic stem cell transplantation. Blood 2004; 103: 3603–3605.

    CAS  PubMed  Google Scholar 

  11. Woywodt A, Schroeder M, Gwinner W, Mengel M, Jaeger M, Schwarz A et al. Elevated numbers of circulating endothelial cells in renal transplant recipients. Transplantation 2003; 76: 1–4.

    PubMed  Google Scholar 

  12. Woywodt A, Blann AD, Kirsch T, Erdbruegger U, Banzet N, Haubitz M et al. Isolation and enumeration of circulating endothelial cells by immunomagnetic isolation: proposal of a definition and a consensus protocol. J Thromb Haemost 2006; 4: 671–677.

    CAS  PubMed  Google Scholar 

  13. George F, Brouqui P, Boffa MC, Mutin M, Drancourt M, Brisson C et al. Demonstration of Rickettsia conorii-induced endothelial injury in vivo by measuring circulating endothelial cells, thrombomodulin, and von Willebrand factor in patients with Mediterranean spotted fever. Blood 1993; 82: 2109–2116.

    CAS  PubMed  Google Scholar 

  14. Dignat-George F, Sampol J . Circulating endothelial cells in vascular disorders: new insights into an old concept. Eur J Haematol 2000; 65: 215–220.

    CAS  PubMed  Google Scholar 

  15. Dignat-George F, Sampol J, Lip G, Blann AD . Circulating endothelial cells: realities and promises in vascular disorders. Pathophysiol Haemost Thromb 2003; 33: 495–499.

    PubMed  Google Scholar 

  16. Heil M, Eitenmuller I, Schmitz-Rixen T, Schaper W . Arteriogenesis versus angiogenesis: similarities and differences. J Cell Mol Med 2006; 10: 45–55.

    CAS  PubMed  Google Scholar 

  17. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964–967.

    CAS  PubMed  Google Scholar 

  18. Cleaver O, Melton DA . Endothelial signaling during development. Nat Med 2003; 9: 661–668.

    CAS  PubMed  Google Scholar 

  19. Risau W . Mechanisms of angiogenesis. Nature 1997; 386: 671–674.

    CAS  PubMed  Google Scholar 

  20. Conway EM, Collen D, Carmeliet P . Molecular mechanisms of blood vessel growth. Cardiovasc Res 2001; 49: 507–521.

    CAS  PubMed  Google Scholar 

  21. Deindl E, Schaper W . The art of arteriogenesis. Cell Biochem Biophys 2005; 43: 1–15.

    CAS  PubMed  Google Scholar 

  22. Fujiyama S, Amano K, Uehira K, Yoshida M, Nishiwaki Y, Nozawa Y 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 2003; 93: 980–989.

    CAS  PubMed  Google Scholar 

  23. Aicher A, Zeiher AM, Dimmeler S . Mobilizing endothelial progenitor cells. Hypertension 2005; 45: 321–325.

    CAS  PubMed  Google Scholar 

  24. Moldovan NI . Tissular insemination of progenitor endothelial cells: the problem, and a suggested solution. Adv Exp Med Biol 2003; 522: 99–113.

    PubMed  Google Scholar 

  25. Ohki Y, Heissig B, Sato Y, Akiyama H, Zhu Z, Hicklin DJ et al. Granulocyte colony-stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils. FASEB J 2005; 19: 2005–2007.

    CAS  PubMed  Google Scholar 

  26. Awad O, Dedkov EI, Jiao C, Bloomer S, Tomanek RJ, Schatteman GC . Differential healing activities of CD34+ and CD14+ endothelial cell progenitors. Arterioscler Thromb Vasc Biol 2006; 26: 758–764.

    CAS  PubMed  Google Scholar 

  27. Anghelina M, Krishnan P, Moldovan L, Moldovan NI . Monocytes/macrophages cooperate with progenitor cells during neovascularization and tissue repair: conversion of cell columns into fibrovascular bundles. Am J Pathol 2006; 168: 529–541.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Blann AD, Pretorius A . Circulating endothelial cells and endothelial progenitor cells: two sides of the same coin, or two different coins? Atherosclerosis 2006; 188: 12–18.

    CAS  PubMed  Google Scholar 

  29. Wassmann S, Werner N, Czech T, Nickenig G . Improvement of endothelial function by systemic transfusion of vascular progenitor cells. Circ Res 2006; 99: e74–e83.

    CAS  PubMed  Google Scholar 

  30. Zengin E, Chalajour F, Gehling UM, Ito WD, Treede H, Lauke H et al. Vascular wall resident progenitor cells: a source for postnatal vasculogenesis. Development 2006; 133: 1543–1551.

    CAS  PubMed  Google Scholar 

  31. Yoon CH, Hur J, Park KW, Kim JH, Lee CS, Oh IY et al. Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells: the role of angiogenic cytokines and matrix metalloproteinases. Circulation 2005; 112: 1618–1627.

    PubMed  Google Scholar 

  32. De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS, Sampaolesi M et al. Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 2005; 8: 211–226.

    CAS  PubMed  Google Scholar 

  33. Fazel S, Cimini M, Chen L, Li S, Angoulvant D, Fedak P et al. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest 2006; 116: 1865–1877.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Grunewald M, Avraham I, Dor Y, Bachar-Lustig E, Itin A, Jung S et al. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 2006; 124: 175–189.

    CAS  PubMed  Google Scholar 

  35. Jin DK, Shido K, Kopp HG, Petit I, Shmelkov SV, Young LM et al. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nat Med 2006; 12: 557–567.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Luo Y, Zhou H, Krueger J, Kaplan C, Lee SH, Dolman C et al. Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest 2006; 116: 2132–2141.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Okamoto R, Ueno M, Yamada Y, Takahashi N, Sano H, Suda T et al. Hematopoietic cells regulate the angiogenic switch during tumorigenesis. Blood 2005; 105: 2757–2763.

    Article  CAS  PubMed  Google Scholar 

  38. O'Neill TJt, Wamhoff BR, Owens GK, Skalak TC . Mobilization of bone marrow-derived cells enhances the angiogenic response to hypoxia without transdifferentiation into endothelial cells. Circ Res 2005; 97: 1027–1035.

    CAS  PubMed  Google Scholar 

  39. Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, Li F et al. Re-defining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 2007; 109: 1801–1809.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Carmeliet P . Angiogenesis in health and disease. Nat Med 2003; 9: 653–660.

    CAS  PubMed  Google Scholar 

  41. Hiraoka N, Allen E, Apel IJ, Gyetko MR, Weiss SJ . Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. Cell 1998; 95: 365–377.

    CAS  PubMed  Google Scholar 

  42. McCawley LJ, Matrisian LM . Matrix metalloproteinases: they're not just for matrix anymore!. Curr Opin Cell Biol 2001; 13: 534–540.

    CAS  PubMed  Google Scholar 

  43. Stetler-Stevenson WG . Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest 1999; 103: 1237–1241.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. You D, Waeckel L, Ebrahimian TG, Blanc-Brude O, Foubert P, Barateau V et al. Increase in vascular permeability and vasodilation are critical for proangiogenic effects of stem cell therapy. Circulation 2006; 114: 328–338.

    PubMed  Google Scholar 

  45. Zentilin L, Tafuro S, Zacchigna S, Arsic N, Pattarini L, Sinigaglia M et al. Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels. Blood 2006; 107: 3546–3554.

    CAS  PubMed  Google Scholar 

  46. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. New Engl J Med 2003; 348: 593–600.

    PubMed  Google Scholar 

  47. Ito H, Rovira II, Bloom ML, Takeda K, Ferrans VJ, Quyyumi AA et al. Endothelial progenitor cells as putative targets for angiostatin. Cancer Res 1999; 59: 5875–5877.

    CAS  PubMed  Google Scholar 

  48. Loomans CJ, de Koning EJ, Staal FJ, Rookmaaker MB, Verseyden C, de Boer HC et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 2004; 53: 195–199.

    CAS  PubMed  Google Scholar 

  49. Palange P, Testa U, Huertas A, Calabro L, Antonucci R, Petrucci E et al. Circulating haemopoietic and endothelial progenitor cells are decreased in COPD. Eur Resp J 2006; 27: 529–541.

    CAS  Google Scholar 

  50. Valgimigli M, Rigolin GM, Fucili A, Porta MD, Soukhomovskaia O, Malagutti P et al. CD34+ and endothelial progenitor cells in patients with various degrees of congestive heart failure. Circulation 2004; 110: 1209–1212.

    CAS  PubMed  Google Scholar 

  51. Grisar J, Aletaha D, Steiner CW, Kapral T, Steiner S, Seidinger D et al. Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis. Circulation 2005; 111: 204–211.

    PubMed  Google Scholar 

  52. George J, Goldstein E, Abashidze S, Deutsch V, Shmilovich H, Finkelstein A et al. Circulating endothelial progenitor cells in patients with unstable angina: association with systemic inflammation. Eur Heart J 2004; 25: 1003–1008.

    CAS  PubMed  Google Scholar 

  53. Massa M, Rosti V, Ferrario M, Campanelli R, Ramajoli I, Rosso R et al. Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood 2005; 105: 199–206.

    CAS  PubMed  Google Scholar 

  54. Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 2001; 103: 2776–2779.

    CAS  PubMed  Google Scholar 

  55. Asahara T, Kawamoto A . Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol 2004; 287: C572–C579.

    CAS  PubMed  Google Scholar 

  56. Honold J, Assmus B, Lehman R, Zeiher AM, Dimmeler S . Stem cell therapy of cardiac disease: an update. Nephrol Dial Transplant 2004; 19: 1673–1677.

    PubMed  Google Scholar 

  57. Rafii S, Lyden D . Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 2003; 9: 702–712.

    CAS  PubMed  Google Scholar 

  58. Urbich C, Dimmeler S . Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 2004; 95: 343–353.

    CAS  PubMed  Google Scholar 

  59. Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R et al. Transcoronary transplantation of progenitor cells after myocardial infarction. New Engl J Med 2006; 355: 1222–1232.

    CAS  PubMed  Google Scholar 

  60. Leor J, Marber M . Endothelial progenitors: a new Tower of Babel? J Am Coll Cardiol 2006; 48: 1588–1590.

    PubMed  Google Scholar 

  61. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. New Engl J Med 2006; 355: 1199–1209.

    CAS  PubMed  Google Scholar 

  62. Rosenzweig A . Cardiac cell therapy – mixed results from mixed cells. New Engl J Med 2006; 355: 1274–1277.

    CAS  PubMed  Google Scholar 

  63. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. New Engl J Med 2006; 355: 1210–1221.

    CAS  PubMed  Google Scholar 

  64. Schwartz RS . The politics and promise of stem-cell research. New Engl J Med 2006; 355: 1189–1191.

    CAS  PubMed  Google Scholar 

  65. Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 2001; 108: 391–397.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Dimmeler S, Zeiher AM . Endothelial cell apoptosis in angiogenesis and vessel regression. Circ Res 2000; 87: 434–439.

    CAS  PubMed  Google Scholar 

  67. Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 2000; 97: 3422–3427.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 1999; 18: 3964–3972.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Gehling UM, Ergun S, Schumacher U, Wagener C, Pantel K, Otte M et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood 2000; 95: 3106–3112.

    CAS  PubMed  Google Scholar 

  70. Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Uchida S, Masuda H et al. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 2001; 103: 634–637.

    CAS  PubMed  Google Scholar 

  71. Rehman J, Li J, Orschell CM, March KL . Peripheral blood ‘endothelial progenitor cells’ are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 2003; 107: 1164–1169.

    PubMed  Google Scholar 

  72. Rehman J, Li J, Parvathaneni L, Karlsson G, Panchal VR, Temm CJ et al. Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells. J Am Coll Cardiol 2004; 43: 2314–2318.

    PubMed  Google Scholar 

  73. Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 2001; 89: E1–E7.

    CAS  PubMed  Google Scholar 

  74. Adams V, Lenk K, Linke A, Lenz D, Erbs S, Sandri M et al. Increase of circulating endothelial progenitor cells in patients with coronary artery disease after exercise-induced ischemia. Arterioscler Thromb Vasc Biol 2004; 24: 684–690.

    CAS  PubMed  Google Scholar 

  75. Eizawa T, Murakami Y, Matsui K, Takahashi M, Muroi K, Amemiya M et al. Circulating endothelial progenitor cells are reduced in hemodialysis patients. Curr Med Res Opin 2003; 19: 627–633.

    PubMed  Google Scholar 

  76. Lambiase PD, Edwards RJ, Anthopoulos P, Rahman S, Meng YG, Bucknall CA et al. Circulating humoral factors and endothelial progenitor cells in patients with differing coronary collateral support. Circulation 2004; 109: 2986–2992.

    PubMed  Google Scholar 

  77. Sandri M, Adams V, Gielen S, Linke A, Lenk K, Krankel N et al. Effects of exercise and ischemia on mobilization and functional activation of blood-derived progenitor cells in patients with ischemic syndromes: results of 3 randomized studies. Circulation 2005; 111: 3391–3399.

    PubMed  Google Scholar 

  78. Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002; 106: 2781–2786.

    PubMed  Google Scholar 

  79. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002; 106: 3009–3017.

    PubMed  Google Scholar 

  80. Lin Y, Weisdorf DJ, Solovey A, Hebbel RP . Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 2000; 105: 71–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Ingram DA, Mead LE, Tanaka H, Meade V, Fenoglio A, Mortell K et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood 2004; 104: 2752–2760.

    CAS  PubMed  Google Scholar 

  82. Ingram DA, Mead LE, Moore DB, Woodard W, Fenoglio A, Yoder MC . Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells. Blood 2005; 105: 2783–2786.

    CAS  PubMed  Google Scholar 

  83. Gulati R, Jevremovic D, Peterson TE, Chatterjee S, Shah V, Vile RG et al. Diverse origin and function of cells with endothelial phenotype obtained from adult human blood. Circ Res 2003; 93: 1023–1025.

    CAS  PubMed  Google Scholar 

  84. Hur J, Yoon CH, Kim HS, Choi JH, Kang HJ, Hwang KK et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol 2004; 24: 288–293.

    CAS  PubMed  Google Scholar 

  85. Stevens T, Rosenberg R, Aird W, Quertermous T, Johnson FL, Garcia JG et al. NHLBI workshop report: endothelial cell phenotypes in heart, lung, and blood diseases. Am J Physiol Cell Physiol 2001; 281: C1422–C1433.

    CAS  PubMed  Google Scholar 

  86. Ingram DA, Caplice NM, Yoder MC . Unresolved questions, changing definitions, and novel paradigms for defining endothelial progenitor cells. Blood 2005; 106: 1525–1531.

    CAS  PubMed  Google Scholar 

  87. Bryder D, Rossi DJ, Weissman IL . Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol 2006; 169: 338–346.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Miller A, Van Zant G . Advances in hematopoietic stem cell research through mouse genetics. Curr Opin Hematol 2006; 13: 209–215.

    PubMed  Google Scholar 

  89. Enis DR, Shepherd BR, Wang Y, Qasim A, Shanahan CM, Weissberg PL et al. Induction, differentiation, and remodeling of blood vessels after transplantation of Bcl-2-transduced endothelial cells. Proc Natl Acad Sci USA 2005; 102: 425–430.

    CAS  PubMed  Google Scholar 

  90. Schechner JS, Nath AK, Zheng L, Kluger MS, Hughes CC, Sierra-Honigmann MR et al. In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. Proc Natl Acad Sci USA 2000; 97: 9191–9196.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Guven H, Shepherd RM, Bach RG, Capoccia BJ, Link DC . The number of endothelial progenitor cell colonies in the blood is increased in patients with angiographically significant coronary artery disease. J Am Coll Cardiol 2006; 48: 1579–1587.

    PubMed  Google Scholar 

  92. Verfaillie CM . Hematopoietic stem cells for transplantation. Nat Immunol 2002; 3: 314–317.

    CAS  PubMed  Google Scholar 

  93. Hess DA, Wirthlin L, Craft TP, Herrbrich PE, Hohm SA, Lahey R et al. Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. Blood 2006; 107: 2162–2169.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Jansen J, Hanks S, Thompson JM, Dugan MJ, Akard LP . Transplantation of hematopoietic stem cells from the peripheral blood. J Cell Mol Med 2005; 9: 37–50.

    PubMed  PubMed Central  Google Scholar 

  95. Ziegler BL, Valtieri M, Porada GA, De Maria R, Muller R, Masella B et al. KDR receptor: a key marker defining hematopoietic stem cells. Science 1999; 285: 1553–1558.

    CAS  PubMed  Google Scholar 

  96. Adams GB, Scadden DT . The hematopoietic stem cell in its place. Nat Immunol 2006; 7: 333–337.

    CAS  PubMed  Google Scholar 

  97. Shizuru JA, Negrin RS, Weissman IL . Hematopoietic stem and progenitor cells: clinical and preclinical regeneration of the hematolymphoid system. Annu Rev Med 2005; 56: 509–538.

    CAS  PubMed  Google Scholar 

  98. Garmy-Susini B, Varner JA . Circulating endothelial progenitor cells. Br J Cancer 2005; 93: 855–858.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000; 95: 952–958.

    CAS  PubMed  Google Scholar 

  100. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A et al. Circulating endothelial progenitor cells and cardiovascular outcomes. New Engl J Med 2005; 353: 999–1007.

    CAS  PubMed  Google Scholar 

  101. Akashi K, Weissman IL . Stem cells and hematolymphoid development. In: Zon LI (ed). Oxford University Press: New York, 2001, pp 15–34.

  102. Eizawa T, Ikeda U, Murakami Y, Matsui K, Yoshioka T, Takahashi M et al. Decrease in circulating endothelial progenitor cells in patients with stable coronary artery disease. Heart 2004; 90: 685–686.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005; 111: 2981–2987.

    PubMed  Google Scholar 

  104. Rohde E, Malischnik C, Thaler D, Maierhofer T, Linkesch W, Lanzer G et al. Blood monocytes mimic endothelial progenitor cells. Stem Cells 2006; 24: 357–367.

    PubMed  Google Scholar 

  105. Schmeisser A, Garlichs CD, Zhang H, Eskafi S, Graffy C, Ludwig J et al. Monocytes coexpress endothelial and macrophagocytic lineage markers and form cord-like structures in Matrigel under angiogenic conditions. Cardiovasc Res 2001; 49: 671–680.

    CAS  PubMed  Google Scholar 

  106. Harraz M, Jiao C, Hanlon HD, Hartley RS, Schatteman GC . CD34-blood-derived human endothelial cell progenitors. Stem Cells 2001; 19: 304–312.

    CAS  PubMed  Google Scholar 

  107. Walenta K, Friedrich EB, Sehnert F, Werner N, Nickenig G . In vitro differentiation characteristics of cultured human mononuclear cells – implications for endothelial progenitor cell biology. Biochem Biophys Res Commun 2005; 333: 476–482.

    CAS  PubMed  Google Scholar 

  108. Zhang SJ, Zhang H, Wei YJ, Su WJ, Liao ZK, Hou M et al. Adult endothelial progenitor cells from human peripheral blood maintain monocyte/macrophage function throughout in vitro culture. Cell Res 2006; 6: 577–584.

    Google Scholar 

  109. Handin RI, Lux SE, Stossel TP (eds) Blood: Principles and Practice of Hematology. JB Lippincott Co: Philadelphia, 1995, p 15.

    Google Scholar 

  110. Grant MB, May WS, Caballero S, Brown GA, Guthrie SM, Mames RN et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med 2002; 8: 607–612.

    CAS  PubMed  Google Scholar 

  111. Cogle CR, Wainman DA, Jorgensen ML, Guthrie SM, Mames RN, Scott EW . Adult human hematopoietic cells provide functional hemangioblast activity. Blood 2004; 103: 133–135.

    CAS  PubMed  Google Scholar 

  112. Gunsilius E, Duba HC, Petzer AL, Kahler CM, Grunewald K, Stockhammer G et al. Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells. Lancet 2000; 355: 1688–1691.

    CAS  PubMed  Google Scholar 

  113. Mesa RA . Clinical and scientific advances in the Philadelphia-chromosome negative chronic myeloproliferative disorders. Int J Hematol 2002; 76: 193–203.

    PubMed  Google Scholar 

  114. Kralovics R, Guan Y, Prchal JT . Acquired uniparental disomy of chromosome 9p is a frequent stem cell defect in polycythemia vera. Exp Hematol 2002; 30: 229–236.

    CAS  PubMed  Google Scholar 

  115. Oppliger Leibundgut E, Horn MP, Brunold C, Pfanner-Meyer B, Marti D, Hirsiger H et al. Hematopoietic and endothelial progenitor cell trafficking in patients with myeloproliferative diseases. Haematologica 2006; 91: 1465–1472.

    PubMed  Google Scholar 

  116. Arras M, Ito WD, Scholz D, Winkler B, Schaper J, Schaper W . Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb. J Clin Invest 1998; 101: 40–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Johnson C, Sung HJ, Lessner SM, Fini ME, Galis ZS . Matrix metalloproteinase-9 is required for adequate angiogenic revascularization of ischemic tissues: potential role in capillary branching. Circ Res 2004; 94: 262–268.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by NINDS P50 NS052606 (DAI), NF043019 Department of Defense (DAI), W81XWH-05-1-0161, Riley Children's Foundation (DAI, MCY), P30 CA82709 (DAI), NIH 1 P01 HL085036 (MCY and DAI), R21 HL088885 NIH/NHLBI (DAI). All authors have no competing financial interests to disclose.

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  1. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA

    D N Prater, J Case, D A Ingram & M C Yoder

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  1. D N Prater
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  2. J Case
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  3. D A Ingram
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  4. M C Yoder
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Correspondence to M C Yoder.

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Prater, D., Case, J., Ingram, D. et al. Working hypothesis to redefine endothelial progenitor cells. Leukemia 21, 1141–1149 (2007). https://doi.org/10.1038/sj.leu.2404676

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  • DOI: https://doi.org/10.1038/sj.leu.2404676

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