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Endothelium

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Human Adult Stem Cells

Part of the book series: Human Cell Culture ((HUCC,volume 7))

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Abstract

Endothelial progenitor cells (EPCs) were first isolated by Asahara [1]. Since then, a new paradigm termed postnatal vascularization, has been proposed to explain the functional contribution of EPCs to vascular repair in various disorders including myocardial infarction, limb ischemia and diabetes. Although vascularization was thought to occur only in the developing fetus [2–4], the finding of circulating EPCs reset the concept of vascularization as de novo formation of vessels and remodeling of the circulatory system in the adult [1]. In vivo functional studies have demonstrated that the recruitment of bone marrow (BM) derived EPC dynamically contributes to neovascularization by two distinct pathways: (1) direct contribution by differentiation into endothelial cells, and (2) indirect contribution by secreting cytokines and modifying the extracellular space [5–15]. Accordingly, EPCs have been broadly accepted as one of the most likely candidate sources for stem cell therapy for vascular disease and as biomarkers to measure the severity of human vascular disorders [16–22].

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References

  1. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275:964–967.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Risau W. Mechanism of angiogenesis. Nature 1997; 386:671–674

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999; 18:3964–3972.

    Article  PubMed  CAS  Google Scholar 

  7. Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999; 5:434–438.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  Google Scholar 

  15. 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 not incorporated into the newly formed vessel. Blood 2006; 107:3546–3554.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Shatteman GC. Adult bone marrow-derived hemangioblasts, endothelial progenitors, and EPCs. Curr Top Dev Biol 2004; 64:141–180.

    Article  Google Scholar 

  19. Iwami Y, Masuda H, Asahara T. Endothelial progenitor cells: past, state of the art, and future. J Cell Mol Med 2004; 8:488–497.

    Article  PubMed  Google Scholar 

  20. Hristov M, Weber C. Endothelial progenitor cells: characterization, pathophysilogy, and possible clinical relevance. J Cell Mol Med 2004; 8:498–508.

    Article  PubMed  Google Scholar 

  21. Blann AD. Assessment of endothelial dysfunction: focus on atherothrombotic disease. Pathophysiol Haemost Thromb 2003; 33:256–261.

    Article  PubMed  Google Scholar 

  22. Quilici J, Banzet N, Paule P et al. Circulating endothelial cell counting as a diagnostic marker for non-ST-elevation acute coronary syndromes. Circulation 2004; 110:1586–1591.

    Google Scholar 

  23. Prater DN, Case J, Ingram DA, Yoder MC. Working hypothesis to redefine endothelial progenitor cells. Leukemia 2007; 21:1141–1149.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  Google Scholar 

  25. 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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  27. 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.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    PubMed  CAS  Google Scholar 

  29. Ishikawa M, Asahara T. Endothelial progenitor cell culture for vascular regeneration. Stem Cells Dev 2004; 13:344–349.

    Article  PubMed  Google Scholar 

  30. 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.

    PubMed  CAS  Google Scholar 

  31. 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.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  33. 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.

    Article  PubMed  Google Scholar 

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

    Google Scholar 

  35. 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.

    Article  PubMed  Google Scholar 

  36. Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R et al. Transcoronory transplantation of progenitor cells after myocardial infarction. New Engl J Med 2006; 355:1199–1209.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  39. 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.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  41. 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.

    Article  PubMed  CAS  Google Scholar 

  42. 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.

    Article  PubMed  CAS  Google Scholar 

  43. Ingram DA, Mead LE, Tanaka H, Mead 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.

    Article  PubMed  CAS  Google Scholar 

  44. 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.

    Article  PubMed  CAS  Google Scholar 

  45. 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.

    Google Scholar 

  46. 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.

    Article  PubMed  CAS  Google Scholar 

  47. Enis DR, Shepherd BR, Wang Y, Qasim A, Shanahan CM, Weissberd 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.

    Article  PubMed  CAS  Google Scholar 

  48. 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.

    Article  PubMed  Google Scholar 

  49. 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.

    PubMed  CAS  Google Scholar 

  50. 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.

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  53. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Böhm M, Nickenig G. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005; 353:999–1007.

    Article  PubMed  CAS  Google Scholar 

  54. 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.

    Article  PubMed  CAS  Google Scholar 

  55. 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.

    Article  PubMed  Google Scholar 

  56. Bailey AS, Willenbring H, Jiang S, Anderson DA, Schroeder DA, Wong MH, Grompe M, Fleming WH. Myeloid lineage progenitors give rise to vascular endothelium. Proc Natl Acad Sci USA 2006; 103(35):13156–13161.

    Article  PubMed  CAS  Google Scholar 

  57. Fazel S, Cimini M, Chen L, Li S, Angoulvant D, Fedak P, Verma S, Weisel RD, Keating A, Li RK. Cardioprotective c-Kit+ cells are from the bone marrow and regulate the myocardial balance of cytokines. J Clin Invest 2006; 116(7):1865–1877.

    Article  PubMed  CAS  Google Scholar 

  58. Balsam LB, Wager AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC. Hematopoietic stem cells adopt mature hematopoietic fates in ischemic myocardium. Nature 2004; 428(6983):668–673.

    Article  PubMed  CAS  Google Scholar 

  59. Chakroborty D, Chowdhury UR, Sarkar C, Baral R, Dasgupta PS, Basu S. Dopamine regulates endothelial progenitor cell mobilization from mouse bone marrow in tumor vascularization. J Clin Invest 2008; 118(4):1380–1389.

    Article  PubMed  CAS  Google Scholar 

  60. Tanaka R, Wada M, Kwon SM, Masuda H, Carr J, Ito R, Miyasaka M, Warren SM, Asahara T, Tepper OM. The effects of flap ischemia on normal and diabetic progenitor cell function. Plast Reconstr Surg 2008; 121(6):1929–1942.

    Article  PubMed  CAS  Google Scholar 

  61. Kwon SM, Eguchi M, Wada M, Iwami Y, Hozumi K, Iwaguro H, Masuda H, Kawamoto A, Asahara T. Specific Jagged-1 signal from bone marrow microenvironment is required for endothelial progenitor cell development for neovascularization. Circulation 2008; 118(2): 157–165.

    Article  PubMed  Google Scholar 

  62. Kato M, Masuda K, Kakugawa K, Kawamoto H, Mugishima H, Katsura Y. Quantification of progenitors capable of generating T cells in human cord blood. Eur J Haematol. 2008; 80:151–159.

    Article  PubMed  CAS  Google Scholar 

  63. Iwaguro H, Yamaguchi J, Kalka C, Murasawa S, Masuda H, Hayashi S, Silver M, Li T, Isner JM, Asahara T. Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation 2002; 105(6):732–738.

    Article  PubMed  CAS  Google Scholar 

  64. Kong D, Melo LG, Mangi AA, Zhang L, Lopez-Ilasaca M, Perrella MA, Liew CC, Pratt RE, Dzau VJ. Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation 2004; 109(14):1769–1775.

    Article  PubMed  CAS  Google Scholar 

  65. Murasawa S, Llevadot J, Silver M, Isner JM, Losordo DW, Asahara T. Constitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells. Circulation 2002; 106(9):1133–1139.

    Article  PubMed  CAS  Google Scholar 

  66. Kusano KF, Pola R, Murayama T, Curry C, Kawamoto A, Iwakura A, Shintani S, Ii M, Asai J et al. Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling. Nat Med 2005; 11(11):1197–1204.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan

    Sangmo Kwon & Takayuki Asahara

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  1. Sangmo Kwon
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  2. Takayuki Asahara
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Editors and Affiliations

  1. University College London Inst. Urology & Nephrology, 67 Riding House Street, London, United Kingdom W1P 7PN

    John R. Masters

  2. Dept. Bioengineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0412, USA

    Bernhard Ø. Palsson

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Kwon, S., Asahara, T. (2009). Endothelium. In: Masters, J.R., Palsson, B.Ø. (eds) Human Adult Stem Cells. Human Cell Culture, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2269-1_3

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