Advertisement

Endothelial Progenitor Cell Therapy in Stroke

  • Yaying Song
  • Zhijun Zhang
  • Guo-Yuan YangEmail author
Chapter

Abstract

Endothelial progenitor cells (EPCs) are unique stem cells in circulating blood. Studies showed strong beneficial evidence using EPC therapy in experimental animal models and clinical trials. In this review, we discussed the characteristics of EPCs in the stroke therapy. We summarized the effect of EPCs on the treatment of cerebrovascular diseases including ischemic and hemorrhagic stroke, moyamoya disease, and vascular tumor, etc. Although the molecular mechanisms of EPC therapy are not fully understood, the function of EPCs included releasing growth factors, regulating microenvironment in the injury territory, and maintaining blood-brain barrier integrity. Clinical application of stem cell-based therapy is still in its infancy. The next decade of EPC research in the stroke field needs to focus on the studying the molecular mechanism or combining other type stem cells to enhance the potential of this therapeutic avenue, and translate to clinical application.

Keywords

Blood-brain barrier EPC Ischemia Stroke Therapy 

Abbreviations

BAVMs

Brain arteriovenous malformations

BBB

Blood-brain barrier

BM

Bone marrow

EOCs

Endothelial outgrowth cells

EPCs

Endothelial progenitor cells

ESCs

Embryonic stem cells

GCSFs

Granulocyte colony-stimulating factors

HCC

Hepatocellular carcinoma

HGF

Hepatocyte growth factor

hUCB

Human umbilical cord blood

MIF

Macrophage migration inhibitory factor

MSCs

Mesenchymal stem cells

NIHSS

NIH Stroke Scale

NSCs

Neural stem cells

OGD

Oxygen glucose depletion

SMPCs

Smooth muscle progenitor cells

tPA

Tissue plasminogen activator

Notes

Acknowledgments

This study was supported by research grants from the National Natural Science Foundation of China (#81471178 and #U1232205 GYY), the Science and Technology Commission of Shanghai Municipality (#13ZR1422600 ZJZ), and KC Wong Foundation (GYY).

References

  1. 1.
    Moretti A, Ferrari F, Villa RF. Neuroprotection for ischaemic stroke: current status and challenges. Pharmacol Ther. 2015;146:23–34.PubMedCrossRefGoogle Scholar
  2. 2.
    Troidl K, Schaper W. Arteriogenesis versus angiogenesis in peripheral artery disease. Diabetes Metab Res Rev. 2012;28 Suppl 1:27–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Liu J, et al. Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials. Prog Neurobiol. 2014;115:138–56.PubMedCrossRefGoogle Scholar
  4. 4.
    Ohab JJ, Carmichael ST. Poststroke neurogenesis: emerging principles of migration and localization of immature neurons. Neuroscientist. 2008;14(4):369–80.PubMedCrossRefGoogle Scholar
  5. 5.
    Ohab JJ, et al. A neurovascular niche for neurogenesis after stroke. J Neurosci. 2006;26(50):13007–16.PubMedCrossRefGoogle Scholar
  6. 6.
    Vallon M, et al. Developmental and pathological angiogenesis in the central nervous system. Cell Mol Life Sci. 2014;71(18):3489–506.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Ma F, et al. Endothelial progenitor cells and revascularization following stroke. Brain Res. 2015;1623:150–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Darby DG, et al. Pathophysiological topography of acute ischemia by combined diffusion-weighted and perfusion MRI. Stroke. 1999;30(10):2043–52.PubMedCrossRefGoogle Scholar
  9. 9.
    Janowski M, Wagner DC, Boltze J. Stem cell-based tissue replacement after stroke: factual necessity or notorious fiction? Stroke. 2015;46(8):2354–63.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Pelliccia F, et al. Endothelial progenitor cells predict long-term prognosis in patients with stable angina treated with percutaneous coronary intervention: five-year follow-up of the PROCREATION study. Circ J. 2013;77(7):1728–35.PubMedCrossRefGoogle Scholar
  11. 11.
    Sobrino T, et al. Increased levels of circulating endothelial progenitor cells in patients with ischaemic stroke treated with statins during acute phase. Eur J Neurol. 2012;19(12):1539–46.PubMedCrossRefGoogle Scholar
  12. 12.
    Ni G, et al. Increased levels of circulating SDF-1alpha and CD34+ CXCR4+ cells in patients with moyamoya disease. Eur J Neurol. 2011;18(11):1304–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Yip HK, et al. Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke. Crit Care. 2011;15(1):R40.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Asahara T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Shi Q, et al. Evidence for circulating bone marrow-derived endothelial cells. Blood. 1998;92(2):362–7.PubMedGoogle Scholar
  16. 16.
    Takahashi T, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999;5(4):434–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Xiao Q, et al. Endothelial progenitor cells, cardiovascular risk factors, cytokine levels and atherosclerosis – results from a large population-based study. PLoS ONE. 2007;2(10):e975.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Fadini GP, et al. Endothelial progenitor cells in the natural history of atherosclerosis. Atherosclerosis. 2007;194(1):46–54.PubMedCrossRefGoogle Scholar
  19. 19.
    Bailey AS, et al. Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells. Blood. 2004;103(1):13–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Flamme I, Risau W. Induction of vasculogenesis and hematopoiesis in vitro. Development. 1992;116(2):435–9.PubMedGoogle Scholar
  21. 21.
    Hsueh YY, et al. Synergy of endothelial and neural progenitor cells from adipose-derived stem cells to preserve neurovascular structures in rat hypoxic-ischemic brain injury. Sci Rep. 2015;5:14985.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Oswald J, et al. Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells. 2004;22(3):377–84.PubMedCrossRefGoogle Scholar
  23. 23.
    Margariti A, et al. Direct reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelialization in tissue-engineered vessels. Proc Natl Acad Sci U S A. 2012;109(34):13793–8.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Murohara T, et al. Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest. 2000;105(11):1527–36.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Vasa M, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001;89(1):E1–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Shintani S, et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation. 2001;103(23):2776–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Bryder D, Rossi DJ, Weissman IL. Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol. 2006;169(2):338–46.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Gehling UM, et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood. 2000;95(10):3106–12.PubMedGoogle Scholar
  29. 29.
    Keller G. Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev. 2005;19(10):1129–55.PubMedCrossRefGoogle Scholar
  30. 30.
    Hristov M, Erl W, Weber PC. Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol. 2003;23(7):1185–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Schaper W, Scholz D. Factors regulating arteriogenesis. Arterioscler Thromb Vasc Biol. 2003;23(7):1143–51.PubMedCrossRefGoogle Scholar
  32. 32.
    Sunderkotter C, et al. Macrophages and angiogenesis. J Leukoc Biol. 1994;55(3):410–22.PubMedGoogle Scholar
  33. 33.
    Kalka C, et al. Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects. Circ Res. 2000;86(12):1198–202.PubMedCrossRefGoogle Scholar
  34. 34.
    Zhang ZG, et al. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res. 2002;90(3):284–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Murohara T. Therapeutic vasculogenesis using human cord blood-derived endothelial progenitors. Trends Cardiovasc Med. 2001;11(8):303–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Kawamoto A, et al. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation. 2001;103(5):634–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Wei MQ, et al. Experimental study of endothelial progenitor cells labeled with superparamagnetic iron oxide in vitro. Mol Med Rep. 2015;11(5):3814–9.PubMedGoogle Scholar
  38. 38.
    Arbab AS, et al. Magnetic resonance imaging and confocal microscopy studies of magnetically labeled endothelial progenitor cells trafficking to sites of tumor angiogenesis. Stem Cells. 2006;24(3):671–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Thebaud NB, et al. Labeling and qualification of endothelial progenitor cells for tracking in tissue engineering: an in vitro study. Int J Artif Organs. 2015;38(4):224–32.PubMedCrossRefGoogle Scholar
  40. 40.
    Aicher A, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation. 2003;107(16):2134–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Lapidot T, Petit I. Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol. 2002;30(9):973–81.PubMedCrossRefGoogle Scholar
  42. 42.
    Tilling L, Chowienczyk P, Clapp B. Progenitors in motion: mechanisms of mobilization of endothelial progenitor cells. Br J Clin Pharmacol. 2009;68(4):484–92.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Ingram DA, et al. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells. Blood. 2005;105(7):2783–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Zhao YH, et al. Endothelial progenitor cells: therapeutic perspective for ischemic stroke. CNS Neurosci Ther. 2013;19(2):67–75.PubMedCrossRefGoogle Scholar
  45. 45.
    Yamashita T, Abe K. Mechanisms of endogenous endothelial repair in stroke. Curr Pharm Des. 2012;18(25):3649–52.PubMedCrossRefGoogle Scholar
  46. 46.
    Navarro-Sobrino M, et al. Mobilization, endothelial differentiation and functional capacity of endothelial progenitor cells after ischemic stroke. Microvasc Res. 2010;80(3):317–23.PubMedCrossRefGoogle Scholar
  47. 47.
    Shen Q, et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science. 2004;304(5675):1338–40.PubMedCrossRefGoogle Scholar
  48. 48.
    Shen L, et al. A novel mechanism for endothelial progenitor cells homing: the SDF-1/CXCR4-Rac pathway may regulate endothelial progenitor cells homing through cellular polarization. Med Hypotheses. 2011;76(2):256–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Li Y, et al. Postacute stromal cell-derived factor-1alpha expression promotes neurovascular recovery in ischemic mice. Stroke. 2014;45(6):1822–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Bogoslovsky T, et al. Stromal-derived factor-1[alpha] correlates with circulating endothelial progenitor cells and with acute lesion volume in stroke patients. Stroke. 2011;42(3):618–25.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Toth ZE, et al. The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow-derived endothelial cells in brains of mice following cerebral ischemia. Blood. 2008;111(12):5544–52.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Pellegrini L, et al. Therapeutic benefit of a combined strategy using erythropoietin and endothelial progenitor cells after transient focal cerebral ischemia in rats. Neurol Res. 2013;35(9):937–47.PubMedCrossRefGoogle Scholar
  53. 53.
    Kielczewski JL, et al. Insulin-like growth factor binding protein-3 mediates vascular repair by enhancing nitric oxide generation. Circ Res. 2009;105(9):897–905.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Ohta T, et al. Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats. Neurosurgery. 2006;59(3):679–86. discussion 679–86.PubMedCrossRefGoogle Scholar
  55. 55.
    Hristov M, et al. Importance of CXC chemokine receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury. Circ Res. 2007;100(4):590–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Walenta KL, et al. Differential chemokine receptor expression regulates functional specialization of endothelial progenitor cell subpopulations. Basic Res Cardiol. 2011;106(2):299–305.PubMedCrossRefGoogle Scholar
  57. 57.
    Ishida Y, et al. Pivotal role of the CCL5/CCR5 interaction for recruitment of endothelial progenitor cells in mouse wound healing. J Clin Invest. 2012;122(2):711–21.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Lin CH, et al. Role of HIF-1alpha-activated Epac1 on HSC-mediated neuroplasticity in stroke model. Neurobiol Dis. 2013;58:76–91.PubMedCrossRefGoogle Scholar
  59. 59.
    Huang PH, et al. Matrix metalloproteinase-9 is essential for ischemia-induced neovascularization by modulating bone marrow-derived endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2009;29(8):1179–84.PubMedCrossRefGoogle Scholar
  60. 60.
    Kanayasu-Toyoda T, et al. Cell-surface MMP-9 protein is a novel functional marker to identify and separate pro-angiogenic cells from early endothelial progenitor cells derived from CD133 cells. Stem Cells. 2016;34(5):1251–62.Google Scholar
  61. 61.
    Cai H, et al. Hypoxia-controlled matrix metalloproteinase-9 hyperexpression promotes behavioral recovery after ischemia. Neurosci Bull. 2015;31(5):550–60.PubMedCrossRefGoogle Scholar
  62. 62.
    Orlic D, et al. Transplanted adult bone marrow cells repair myocardial infarcts in mice. Ann N Y Acad Sci. 2001;938:221–9. discussion 229–30.PubMedCrossRefGoogle Scholar
  63. 63.
    Hayakawa K, et al. Reactive astrocytes promote adhesive interactions between brain endothelium and endothelial progenitor cells via HMGB1 and beta-2 integrin signaling. Stem Cell Res. 2014;12(2):531–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Hayakawa K, et al. High-mobility group box 1 from reactive astrocytes enhances the accumulation of endothelial progenitor cells in damaged white matter. J Neurochem. 2013;125(2):273–80.PubMedCrossRefGoogle Scholar
  65. 65.
    Ball SG, Shuttleworth AC, Kielty CM. Direct cell contact influences bone marrow mesenchymal stem cell fate. Int J Biochem Cell Biol. 2004;36(4):714–27.PubMedCrossRefGoogle Scholar
  66. 66.
    Lemischka IR, Moore KA. Stem cells: interactive niches. Nature. 2003;425(6960):778–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Aguirre A, Planell JA, Engel E. Dynamics of bone marrow-derived endothelial progenitor cell/mesenchymal stem cell interaction in co-culture and its implications in angiogenesis. Biochem Biophys Res Commun. 2010;400(2):284–91.PubMedCrossRefGoogle Scholar
  68. 68.
    Shudo Y, et al. Spatially oriented, temporally sequential smooth muscle cell-endothelial progenitor cell bi-level cell sheet neovascularizes ischemic myocardium. Circulation. 2013;128(11 Suppl 1):S59–68.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Kaneko Y, et al. Cell therapy for stroke: emphasis on optimizing safety and efficacy profile of endothelial progenitor cells. Curr Pharm Des. 2012;18(25):3731–4.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Hoenig MR, Bianchi C, Sellke FW. Hypoxia inducible factor-1 alpha, endothelial progenitor cells, monocytes, cardiovascular risk, wound healing, cobalt and hydralazine: a unifying hypothesis. Curr Drug Targets. 2008;9(5):422–35.PubMedCrossRefGoogle Scholar
  71. 71.
    Kwon HM, et al. Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia. J Clin Invest. 1998;101(8):1551–6.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Feng N, et al. Insulin-like growth factor binding protein-2 promotes adhesion of endothelial progenitor cells to endothelial cells via integrin alpha5beta1. J Mol Neurosci. 2015;57(3):426–34.PubMedCrossRefGoogle Scholar
  73. 73.
    Minami Y, et al. Angiogenic potential of early and late outgrowth endothelial progenitor cells is dependent on the time of emergence. Int J Cardiol. 2015;186:305–14.PubMedCrossRefGoogle Scholar
  74. 74.
    Park KJ, et al. Bone marrow-derived endothelial progenitor cells protect postischemic axons after traumatic brain injury. J Cereb Blood Flow Metab. 2014;34(2):357–66.PubMedCrossRefGoogle Scholar
  75. 75.
    Nakatomi H, et al. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell. 2002;110(4):429–41.PubMedCrossRefGoogle Scholar
  76. 76.
    Jin K, et al. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci U S A. 2002;99(18):11946–50.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Drago J, et al. Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I. Proc Natl Acad Sci U S A. 1991;88(6):2199–203.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Obtulowicz P, et al. Induction of endothelial phenotype from Warton Jelly-derived MSC and comparison of their vaso- and neuro-protective potential with primary WJ-MSC in CA1 hippocampal region ex vivo. Cell Transplant. 2016;25(4):715–27.Google Scholar
  79. 79.
    Peplow PV. Influence of growth factors and cytokines on angiogenic function of endothelial progenitor cells: a review of in vitro human studies. Growth Factors. 2014;32(3–4):83–116.PubMedCrossRefGoogle Scholar
  80. 80.
    Kanzler I, et al. Differential roles of angiogenic chemokines in endothelial progenitor cell-induced angiogenesis. Basic Res Cardiol. 2013;108(1):310.PubMedCrossRefGoogle Scholar
  81. 81.
    Song MB, et al. Transfection of HGF gene enhances endothelial progenitor cell (EPC) function and improves EPC transplant efficiency for balloon-induced arterial injury in hypercholesterolemic rats. Vascul Pharmacol. 2009;51(2–3):205–13.PubMedCrossRefGoogle Scholar
  82. 82.
    Fan Y, et al. Endothelial progenitor cell transplantation improves long-term stroke outcome in mice. Ann Neurol. 2010;67(4):488–97.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Honmou O, et al. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain. 2011;134(Pt 6):1790–807.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Willing AE, et al. Intravenous versus intrastriatal cord blood administration in a rodent model of stroke. J Neurosci Res. 2003;73(3):296–307.PubMedCrossRefGoogle Scholar
  85. 85.
    Chen J, et al. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke. 2001;32(11):2682–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Naruse K, et al. Therapeutic neovascularization using cord blood-derived endothelial progenitor cells for diabetic neuropathy. Diabetes. 2005;54(6):1823–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Danielyan L, et al. Intranasal delivery of cells to the brain. Eur J Cell Biol. 2009;88(6):315–24.PubMedCrossRefGoogle Scholar
  88. 88.
    van Velthoven CT, et al. Nasal administration of stem cells: a promising novel route to treat neonatal ischemic brain damage. Pediatr Res. 2010;68(5):419–22.PubMedGoogle Scholar
  89. 89.
    Moubarik C, et al. Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke. Stem Cell Rev. 2011;7(1):208–20.PubMedCrossRefGoogle Scholar
  90. 90.
    Asahara T, Kawamoto A, Masuda H. Concise review: circulating endothelial progenitor cells for vascular medicine. Stem Cells. 2011;29(11):1650–5.PubMedCrossRefGoogle Scholar
  91. 91.
    Taguchi A, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest. 2004;114(3):330–8.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Perin EC, Willerson JT. CD34+ autologous human stem cells in treating refractory angina. Circ Res. 2011;109(4):351–2.PubMedCrossRefGoogle Scholar
  93. 93.
    Chen YL, et al. Intra-carotid arterial administration of autologous peripheral blood-derived endothelial progenitor cells improves acute ischemic stroke neurological outcomes in rats. Int J Cardiol. 2015;201:668–83.PubMedCrossRefGoogle Scholar
  94. 94.
    Liang CC, et al. The protective effect of human umbilical cord blood CD34+ cells and estradiol against focal cerebral ischemia in female ovariectomized rat: cerebral MR imaging and immunohistochemical study. PLoS ONE. 2016;11(1):e0147133.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Iskander A, et al. Intravenous administration of human umbilical cord blood-derived AC133+ endothelial progenitor cells in rat stroke model reduces infarct volume: magnetic resonance imaging and histological findings. Stem Cells Transl Med. 2013;2(9):703–14.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Hiasa K, et al. Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation. 2004;109(20):2454–61.PubMedCrossRefGoogle Scholar
  97. 97.
    Dong L, et al. Insulin modulates ischemia-induced endothelial progenitor cell mobilization and neovascularization in diabetic mice. Microvasc Res. 2011;82(3):227–36.PubMedCrossRefGoogle Scholar
  98. 98.
    Yu JX, et al. Combination of stromal-derived factor-1alpha and vascular endothelial growth factor gene-modified endothelial progenitor cells is more effective for ischemic neovascularization. J Vasc Surg. 2009;50(3):608–16.PubMedCrossRefGoogle Scholar
  99. 99.
    Qu K, et al. MicroRNAs: key regulators of endothelial progenitor cell functions. Clin Chim Acta. 2015;448:65–73.PubMedCrossRefGoogle Scholar
  100. 100.
    Zheng Y, Xu Z. MicroRNA-22 induces endothelial progenitor cell senescence by targeting AKT3. Cell Physiol Biochem. 2014;34(5):1547–55.PubMedCrossRefGoogle Scholar
  101. 101.
    Cheng BB, et al. MicroRNA-34a targets Forkhead box j2 to modulate differentiation of endothelial progenitor cells in response to shear stress. J Mol Cell Cardiol. 2014;74:4–12.PubMedCrossRefGoogle Scholar
  102. 102.
    Zhang J, et al. microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway. PLoS ONE. 2013;8(12):e83294.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Goretti E, et al. MicroRNA-16 affects key functions of human endothelial progenitor cells. J Leukoc Biol. 2013;93(5):645–55.PubMedCrossRefGoogle Scholar
  104. 104.
    Tabuchi T, et al. MicroRNA-34a regulates the longevity-associated protein SIRT1 in coronary artery disease: effect of statins on SIRT1 and microRNA-34a expression. Clin Sci (Lond). 2012;123(3):161–71.CrossRefGoogle Scholar
  105. 105.
    Meng S, et al. Downregulation of microRNA-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene Spred-1. J Mol Cell Cardiol. 2012;53(1):64–72.PubMedCrossRefGoogle Scholar
  106. 106.
    Meng S, et al. MicroRNA 107 partly inhibits endothelial progenitor cells differentiation via HIF-1beta. PLoS ONE. 2012;7(7):e40323.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Minami Y, et al. Effect of atorvastatin on microRNA 221/222 expression in endothelial progenitor cells obtained from patients with coronary artery disease. Eur J Clin Invest. 2009;39(5):359–67.PubMedCrossRefGoogle Scholar
  108. 108.
    George AL, et al. Endothelial progenitor cell biology in disease and tissue regeneration. J Hematol Oncol. 2011;4:24.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Hur J, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol. 2004;24(2):288–93.PubMedCrossRefGoogle Scholar
  110. 110.
    Akita T, et al. Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization. Lab Invest. 2003;83(1):65–73.PubMedCrossRefGoogle Scholar
  111. 111.
    Sherma AK, Bendok BR. Endothelial progenitor cells in moyamoya disease. Neurosurgery. 2009;64(5):N11.PubMedCrossRefGoogle Scholar
  112. 112.
    Kim JH, et al. Decreased level and defective function of circulating endothelial progenitor cells in children with moyamoya disease. J Neurosci Res. 2010;88(3):510–8.PubMedGoogle Scholar
  113. 113.
    Jung KH, et al. Circulating endothelial progenitor cells as a pathogenetic marker of moyamoya disease. J Cereb Blood Flow Metab. 2008;28(11):1795–803.PubMedCrossRefGoogle Scholar
  114. 114.
    Sugiyama T, et al. Bone marrow-derived endothelial progenitor cells participate in the initiation of moyamoya disease. Neurol Med Chir (Tokyo). 2011;51(11):767–73.CrossRefGoogle Scholar
  115. 115.
    Pereira Lopes FR, et al. Double gene therapy with granulocyte colony-stimulating factor and vascular endothelial growth factor acts synergistically to improve nerve regeneration and functional outcome after sciatic nerve injury in mice. Neuroscience. 2013;230:184–97.PubMedCrossRefGoogle Scholar
  116. 116.
    Kioi M, et al. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest. 2010;120(3):694–705.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Li B, et al. The effect of CXCL12 on endothelial progenitor cells: potential target for angiogenesis in intracerebral hemorrhage. J Interferon Cytokine Res. 2015;35(1):23–31.PubMedCrossRefGoogle Scholar
  118. 118.
    Nandra KK, et al. Pharmacological preconditioning with erythropoietin attenuates the organ injury and dysfunction induced in a rat model of hemorrhagic shock. Dis Model Mech. 2013;6(3):701–9.PubMedCrossRefGoogle Scholar
  119. 119.
    Paczkowska E, et al. Increased circulating endothelial progenitor cells in patients with haemorrhagic and ischaemic stroke: the role of endothelin-1. J Neurol Sci. 2013;325(1–2):90–9.PubMedCrossRefGoogle Scholar
  120. 120.
    Liu P, et al. Rosuvastatin for enhancement of aneurysm neck endothelialization after coil embolization: promotion of endothelial progenitor cells in a rodent model. J Neurosurg. 2016;124(5):1265–74.Google Scholar
  121. 121.
    Asif K, Leschke J, Lazzaro MA. Cerebral arteriovenous malformation diagnosis and management. Semin Neurol. 2013;33(5):468–75.PubMedCrossRefGoogle Scholar
  122. 122.
    Wang L, et al. The role of SDF-1/CXCR4 in the vasculogenesis and remodeling of cerebral arteriovenous malformation. Ther Clin Risk Manag. 2015;11:1337–44.PubMedPubMedCentralGoogle Scholar
  123. 123.
    Gao P, et al. Evidence of endothelial progenitor cells in the human brain and spinal cord arteriovenous malformations. Neurosurgery. 2010;67(4):1029–35.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Lu L, et al. Increased endothelial progenitor cells and vasculogenic factors in higher-staged arteriovenous malformations. Plast Reconstr Surg. 2011;128(4):260e–9.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Ribatti D. The involvement of endothelial progenitor cells in tumor angiogenesis. J Cell Mol Med. 2004;8(3):294–300.PubMedCrossRefGoogle Scholar
  126. 126.
    Rafii S. Circulating endothelial precursors: mystery, reality, and promise. J Clin Invest. 2000;105(1):17–9.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Moschetta M, et al. Role of endothelial progenitor cells in cancer progression. Biochim Biophys Acta. 2014;1846(1):26–39.PubMedGoogle Scholar
  128. 128.
    Marcola M, Rodrigues CE. Endothelial progenitor cells in tumor angiogenesis: another brick in the wall. Stem Cells Int. 2015;2015:832649.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Ammendola M, et al. Targeting endothelial progenitor cells in cancer as a novel biomarker and anti-angiogenic therapy. Curr Stem Cell Res Ther. 2015;10(2):181–7.PubMedCrossRefGoogle Scholar
  130. 130.
    Pirro M, et al. Baseline and post-surgery endothelial progenitor cell levels in patients with early-stage non-small-cell lung carcinoma: impact on cancer recurrence and survival. Eur J Cardiothorac Surg. 2013;44(4):e245–52.PubMedCrossRefGoogle Scholar
  131. 131.
    Zhu H, et al. The mobilization, recruitment and contribution of bone marrow-derived endothelial progenitor cells to the tumor neovascularization occur at an early stage and throughout the entire process of hepatocellular carcinoma growth. Oncol Rep. 2012;28(4):1217–24.PubMedGoogle Scholar
  132. 132.
    Ahn JB, et al. Circulating endothelial progenitor cells (EPC) for tumor vasculogenesis in gastric cancer patients. Cancer Lett. 2010;288(1):124–32.PubMedCrossRefGoogle Scholar
  133. 133.
    Hamanishi J, et al. Activated local immunity by CC chemokine ligand 19-transduced embryonic endothelial progenitor cells suppresses metastasis of murine ovarian cancer. Stem Cells. 2010;28(1):164–73.PubMedGoogle Scholar
  134. 134.
    Althaus J, et al. Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein following focal cerebral ischemia in rats. Neurochem Int. 2006;48(8):687–95.PubMedCrossRefGoogle Scholar
  135. 135.
    Prisco AR et al. TNFalpha regulates endothelial progenitor cell migration via CADM1 and NF-kB. Stem Cells. 2016;34(7):1922–33.Google Scholar
  136. 136.
    Chen C, et al. Effect of HMGB1 on the paracrine action of EPC promotes post-ischemic neovascularization in mice. Stem Cells. 2014;32(10):2679–89.PubMedCrossRefGoogle Scholar
  137. 137.
    Molin DG, van den Akker NM, Post MJ. Affirmative action of osteopontin on endothelial progenitors. Arterioscler Thromb Vasc Biol. 2008;28(12):2099–100.PubMedCrossRefGoogle Scholar
  138. 138.
    Murohara T, et al. Role of endothelial nitric oxide synthase in endothelial cell migration. Arterioscler Thromb Vasc Biol. 1999;19(5):1156–61.PubMedCrossRefGoogle Scholar
  139. 139.
    Yuan Y, et al. Derivation of human peripheral blood derived endothelial progenitor cells and the role of osteopontin surface modification and eNOS transfection. Biomaterials. 2013;34(30):7292–301.PubMedCrossRefGoogle Scholar
  140. 140.
    Pena I, Borlongan CV. Translating G-CSF as an adjunct therapy to stem cell transplantation for stroke. Transl Stroke Res. 2015;6(6):421–9.PubMedCrossRefGoogle Scholar
  141. 141.
    Bai YY, et al. Synergistic effects of transplanted endothelial progenitor cells and RWJ 67657 in diabetic ischemic stroke models. Stroke. 2015;46(7):1938–46.PubMedCrossRefGoogle Scholar
  142. 142.
    Kim YJ, Jung YW. Systemic injection of recombinant human erythropoietin after focal cerebral ischemia enhances oligodendroglial and endothelial progenitor cells in rat brain. Anat Cell Biol. 2010;43(2):140–9.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Chi Y, et al. Detection of cytokines in supernatant from hematopoietic stem/progenitor cells co-cultured with mesenchymal stem cells and endothelial progenitor cells. Cell Tissue Bank. 2014;15(3):397–402.PubMedCrossRefGoogle Scholar
  144. 144.
    Yoon CH, 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(11):1618–27.PubMedCrossRefGoogle Scholar
  145. 145.
    Nih LR, et al. Neuroblast survival depends on mature vascular network formation after mouse stroke: role of endothelial and smooth muscle progenitor cell co-administration. Eur J Neurosci. 2012;35(8):1208–17.PubMedCrossRefGoogle Scholar
  146. 146.
    Daneman R, et al. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature. 2010;468(7323):562–6.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Schwarz SC, Schwarz J. Translation of stem cell therapy for neurological diseases. Transl Res. 2010;156(3):155–60.PubMedCrossRefGoogle Scholar
  148. 148.
    Lasala GP, et al. Combination stem cell therapy for the treatment of medically refractory coronary ischemia: a Phase I study. Cardiovasc Revasc Med. 2011;12(1):29–34.PubMedCrossRefGoogle Scholar
  149. 149.
    Li Q, et al. Silica-coated superparamagnetic iron oxide nanoparticles targeting of EPCs in ischemic brain injury. Biomaterials. 2013;34(21):4982–92.PubMedCrossRefGoogle Scholar
  150. 150.
    Ganju RK, et al. The alpha-chemokine, stromal cell-derived factor-1alpha, binds to the transmembrane G-protein-coupled CXCR-4 receptor and activates multiple signal transduction pathways. J Biol Chem. 1998;273(36):23169–75.PubMedCrossRefGoogle Scholar
  151. 151.
    Oh BJ, et al. Differences in donor CXCR4 expression levels are correlated with functional capacity and therapeutic outcome of angiogenic treatment with endothelial colony forming cells. Biochem Biophys Res Commun. 2010;398(4):627–33.PubMedCrossRefGoogle Scholar
  152. 152.
    Chen J, et al. Endothelial nitric oxide synthase regulates brain-derived neurotrophic factor expression and neurogenesis after stroke in mice. J Neurosci. 2005;25(9):2366–75.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Marti HJ, et al. Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol. 2000;156(3):965–76.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Peplow PV. Growth factor- and cytokine-stimulated endothelial progenitor cells in post-ischemic cerebral neovascularization. Neural Regen Res. 2014;9(15):1425–9.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    He T, et al. Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke. 2004;35(10):2378–84.PubMedCrossRefGoogle Scholar
  156. 156.
    Asahara T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999;85(3):221–8.PubMedCrossRefGoogle Scholar
  157. 157.
    Kawamoto A, et al. Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation. 2003;107(3):461–8.PubMedCrossRefGoogle Scholar
  158. 158.
    Rehman J, et al. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003;107(8):1164–9.PubMedCrossRefGoogle Scholar
  159. 159.
    Nolan DJ, et al. Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev Cell. 2013;26(2):204–19.PubMedCrossRefGoogle Scholar
  160. 160.
    Waltenberger J, Lange J, Kranz A. Vascular endothelial growth factor-A-induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus: a potential predictor for the individual capacity to develop collaterals. Circulation. 2000;102(2):185–90.PubMedCrossRefGoogle Scholar
  161. 161.
    Schanzer A, et al. Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor. Brain Pathol. 2004;14(3):237–48.PubMedCrossRefGoogle Scholar
  162. 162.
    Imitola J, et al. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A. 2004;101(52):18117–22.PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Kokaia Z, Lindvall O. Neurogenesis after ischaemic brain insults. Curr Opin Neurobiol. 2003;13(1):127–32.PubMedCrossRefGoogle Scholar
  164. 164.
    Kahle MP, Bix GJ. Neuronal restoration following ischemic stroke: influences, barriers, and therapeutic potential. Neurorehabil Neural Repair. 2013;27(5):469–78.PubMedCrossRefGoogle Scholar
  165. 165.
    Palmer TD, Willhoite AR, Gage FH. Vascular niche for adult hippocampal neurogenesis. J Comp Neurol. 2000;425(4):479–94.PubMedCrossRefGoogle Scholar
  166. 166.
    Wolswijk G, Riddle PN, Noble M. Platelet-derived growth factor is mitogenic for O-2Aadult progenitor cells. Glia. 1991;4(5):495–503.PubMedCrossRefGoogle Scholar
  167. 167.
    Barres BA, et al. Multiple extracellular signals are required for long-term oligodendrocyte survival. Development. 1993;118(1):283–95.PubMedGoogle Scholar
  168. 168.
    Cameron HA, Hazel TG, McKay RD. Regulation of neurogenesis by growth factors and neurotransmitters. J Neurobiol. 1998;36(2):287–306.PubMedCrossRefGoogle Scholar
  169. 169.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.PubMedCrossRefGoogle Scholar
  170. 170.
    Zhang X, et al. Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway. Biochem Biophys Res Commun. 2013;431(3):404–8.PubMedCrossRefGoogle Scholar
  171. 171.
    Wang S, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15(2):261–71.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Fish JE, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15(2):272–84.PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Chen J, et al. MiR-126 contributes to human umbilical cord blood cell-induced neurorestorative effects after stroke in type-2 diabetic mice. Stem Cells. 2016;34(1):102–13.PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Tano N, Kim HW, Ashraf M. microRNA-150 regulates mobilization and migration of bone marrow-derived mononuclear cells by targeting Cxcr4. PLoS ONE. 2011;6(10):e23114.PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Rolland-Turner M, et al. Adenosine stimulates the migration of human endothelial progenitor cells. Role of CXCR4 and microRNA-150. PLoS ONE. 2013;8(1):e54135.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Wang HW, et al. Deficiency of the microRNA-31-microRNA-720 pathway in the plasma and endothelial progenitor cells from patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2014;34(4):857–69.PubMedCrossRefGoogle Scholar
  177. 177.
    Cheng CC, et al. Genetic module and miRNome trait analyses reflect the distinct biological features of endothelial progenitor cells from different anatomic locations. BMC Genomics. 2012;13:447.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res. 2010;107(9):1047–57.PubMedCrossRefGoogle Scholar
  179. 179.
    Deregibus MC, et al. Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood. 2007;110(7):2440–8.PubMedCrossRefGoogle Scholar
  180. 180.
    Wang J, et al. Effects of endothelial progenitor cell-derived microvesicles on hypoxia/reoxygenation-induced endothelial dysfunction and apoptosis. Oxid Med Cell Longev. 2013;2013:572729.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of Neurology, Shanghai Ruijin Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Neuroscience and Neuroengineering Center, Med-X Research Institute and School, Biomedical EngineeringShanghai Jiao Tong UniversityShanghaiChina

Personalised recommendations