Table of Contents Author Guidelines Submit a Manuscript
Stem Cells International
Volume 2017 (2017), Article ID 2193432, 12 pages
https://doi.org/10.1155/2017/2193432
Review Article

Endothelial Progenitor Cells for Ischemic Stroke: Update on Basic Research and Application

1Department of Neurology, People’s Liberation Army 152 Hospital, Pingdingshan, Henan 467000, China
2Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
3Department of Neurology, General Hospital of Jinan Military Region, Jinan, Shandong 250031, China

Correspondence should be addressed to Zhenhua Zhou; moc.621@100retiolpxe

Received 16 May 2017; Accepted 3 July 2017; Published 16 August 2017

Academic Editor: Yao Li

Copyright © 2017 Shaohua Liao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Gutierrez-Fernandez, L. Otero-Ortega, J. Ramos-Cejudo, B. Rodríguez-Frutos, B. Fuentes, and E. Díez-Tejedor, “Adipose tissue-derived mesenchymal stem cells as a strategy to improve recovery after stroke,” Expert Opinion on Biological Therapy, vol. 15, no. 6, pp. 873–881, 2015. View at Publisher · View at Google Scholar · View at Scopus
  2. D. Mozaffarian, E. J. Benjamin, A. S. Go et al., “Heart disease and stroke statistics—2015 update: a report from the American Heart Association,” Circulation, vol. 131, no. 4, pp. e29–e322, 2015. View at Publisher · View at Google Scholar · View at Scopus
  3. L. Wei, Z. Z. Wei, M. Q. Jiang, O. Mohamad, and S. P. Yu, “Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke,” Progress in Neurobiology, 2017. View at Publisher · View at Google Scholar
  4. Z. M. Chen, R. Collins, L. S. Liu, H. C. Pan, R. Peto, and J. X. Xie, “CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group,” Lancet, vol. 349, no. 9066, pp. 1641–1649, 1997. View at Google Scholar
  5. Z. Wang, J. Li, C. Wang et al., “Gender differences in 1-year clinical characteristics and outcomes after stroke: results from the China National Stroke Registry,” PLoS One, vol. 8, no. 2, article e56459, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. Z. L. Hao, M. Liu, W. Li et al., “Basic characteristics and functional outcomes of 3123 consecutive patients in Chengdu stroke registry,” Chinese Journal of Neurology, vol. 44, no. 12, pp. 826–831, 2011. View at Google Scholar
  7. A. Durukan and T. Tatlisumak, “Acute ischemic stroke: overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia,” Pharmacology, Biochemistry, and Behavior, vol. 87, no. 1, pp. 179–197, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. W. L. Li, S. P. Yu, D. Chen et al., “The regulatory role of NF-kappaB in autophagy-like cell death after focal cerebral ischemia in mice,” Neuroscience, vol. 244, pp. 16–30, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Puyal, V. Ginet, and P. G. Clarke, “Multiple interacting cell death mechanisms in the mediation of excitotoxicity and ischemic brain damage: a challenge for neuroprotection,” Progress in Neurobiology, vol. 105, pp. 24–48, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. L. Wei, D. J. Ying, L. Cui, J. Langsdorf, and S. P. Yu, “Necrosis, apoptosis and hybrid death in the cortex and thalamus after barrel cortex ischemia in rats,” Brain Research, vol. 1022, no. 1-2, pp. 54–61, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Y. Xiao, L. Wei, S. Xia, S. Rothman, and S. P. Yu, “Ionic mechanism of ouabain-induced concurrent apoptosis and necrosis in individual cultured cortical neurons,” The Journal of Neuroscience, vol. 22, no. 4, pp. 1350–1362, 2002. View at Google Scholar
  12. L. Hoyte, J. Kaur, and A. M. Buchan, “Lost in translation: taking neuroprotection from animal models to clinical trials,” Experimental Neurology, vol. 188, no. 2, pp. 200–204, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. I. L. Maier, D. Behme, M. Schnieder et al., “Bridging-therapy with intravenous recombinant tissue plasminogen activator improves functional outcome in patients with endovascular treatment in acute stroke,” Journal of the Neurological Sciences, vol. 372, pp. 300–304, 2017. View at Publisher · View at Google Scholar
  14. N. Wahlgren, N. Ahmed, A. Davalos et al., “Thrombolysis with alteplase 3-4. 5 h after acute ischaemic stroke (SITS-ISTR): an observational study,” Lancet, vol. 372, no. 9646, pp. 1303–1309, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. G. C. Fonarow, E. E. Smith, J. L. Saver et al., “Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes,” Circulation, vol. 123, no. 7, pp. 750–758, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. T. Asahara, T. Murohara, A. Sullivan et al., “Isolation of putative progenitor endothelial cells for angiogenesis,” Science, vol. 275, no. 5302, pp. 964–967, 1997. View at Google Scholar
  17. Y. Fan, F. Shen, T. Frenzel et al., “Endothelial progenitor cell transplantation improves long-term stroke outcome in mice,” Annals of Neurology, vol. 67, no. 4, pp. 488–497, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. F. Du, J. Zhou, X. H. Ren Gong et al., “Endothelial progenitor cells in atherosclerosis,” Frontiers in Bioscience (Landmark Ed), vol. 17, pp. 2327–2349, 2012. View at Google Scholar
  19. T. Lapidot and I. Petit, “Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells,” Experimental Hematology, vol. 30, no. 9, pp. 973–981, 2002. View at Google Scholar
  20. T. Lapidot, A. Dar, and O. Kollet, “How do stem cells find their way home?” Blood, vol. 106, no. 6, pp. 1901–1910, 2005. View at Google Scholar
  21. E. Y. Choi, H. Lee, J. S. Woo et al., “Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals,” Nutrition, vol. 31, no. 9, pp. 1131–1135, 2015. View at Publisher · View at Google Scholar · View at Scopus
  22. H. S. Jeong, S. Kim, S. J. Hong et al., “Black raspberry extract increased circulating endothelial progenitor cells and improved arterial stiffness in patients with metabolic syndrome: a randomized controlled trial,” Journal of Medicinal Food, vol. 19, no. 4, pp. 346–352, 2016. View at Publisher · View at Google Scholar · View at Scopus
  23. S. Y. Wu, J. Mayneris-Perxachs, J. A. Lovegrove, S. Todd, and P. Yaqoob, “Fish-oil supplementation alters numbers of circulating endothelial progenitor cells and microparticles independently of eNOS genotype,” The American Journal of Clinical Nutrition, vol. 100, no. 5, pp. 1232–1243, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. P. H. Huang, Y. H. Chen, H. Y. Tsai et al., “Intake of red wine increases the number and functional capacity of circulating endothelial progenitor cells by enhancing nitric oxide bioavailability,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 4, pp. 869–877, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Gill, S. Dias, K. Hattori et al., “Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells,” Circulation Research, vol. 88, no. 2, pp. 167–174, 2001. View at Google Scholar
  26. F. Bautz, S. Rafii, L. Kanz, and R. Möhle, “Expression and secretion of vascular endothelial growth factor-A by cytokine-stimulated hematopoietic progenitor cells. Possible role in the hematopoietic microenvironment,” Experimental Hematology, vol. 28, no. 6, pp. 700–706, 2000. View at Google Scholar
  27. T. M. Powell, J. D. Paul, J. M. Hill et al., “Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 2, pp. 296–301, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. N. Roberts, Q. Xiao, G. Weir, Q. Xu, and M. Jahangiri, “Endothelial progenitor cells are mobilized after cardiac surgery,” The Annals of Thoracic Surgery, vol. 83, no. 2, pp. 598–605, 2007. View at Google Scholar
  29. R. M. Lemoli and A. D’Addio, “Hematopoietic stem cell mobilization,” Haematologica, vol. 93, no. 3, pp. 321–324, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. W. Bensinger, J. F. DiPersio, and J. M. McCarty, “Improving stem cell mobilization strategies: future directions,” Bone Marrow Transplantation, vol. 43, no. 3, pp. 181–195, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. D. J. Ceradini, A. R. Kulkarni, M. J. Callaghan et al., “Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1,” Nature Medicine, vol. 10, no. 8, pp. 858–864, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. D. H. Walter, J. Haendeler, J. Reinhold et al., “Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease,” Circulation Research, vol. 97, no. 11, pp. 1142–1151, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. T. Asahara and J. M. Isner, “Endothelial progenitor cells for vascular regeneration,” Journal of Hematotherapy & Stem Cell Research, vol. 11, no. 2, pp. 171–178, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Aicher, C. Heeschen, C. Mildner-Rihm et al., “Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells,” Nature Medicine, vol. 9, no. 11, pp. 1370–1376, 2003. View at Google Scholar
  35. A. T. Askari, S. Unzek, Z. B. Popovic et al., “Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy,” Lancet, vol. 362, no. 9385, pp. 697–703, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. C. Urbich, A. Aicher, C. Heeschen et al., “Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells,” Journal of Molecular and Cellular Cardiology, vol. 39, no. 5, pp. 733–742, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. T. Lapidot, “Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull NOD/SCID mice. The role of SDF-1/CXCR4 interactions,” Annals of the New York Academy of Sciences, vol. 938, pp. 83–95, 2001. View at Google Scholar
  38. Y. Fan, J. Ye, F. Shen et al., “Interleukin-6 stimulates circulating blood-derived endothelial progenitor cell angiogenesis in vitro,” Journal of Cerebral Blood Flow and Metabolism, vol. 28, no. 1, pp. 90–98, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. H. Shao, Y. Tan, D. Eton et al., “Statin and stromal cell-derived factor-1 additively promote angiogenesis by enhancement of progenitor cells incorporation into new vessels,” Stem Cells, vol. 26, no. 5, pp. 1376–1384, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Chen and J. A. Lopez, “Interactions of platelets with subendothelium and endothelium,” Microcirculation, vol. 12, no. 3, pp. 235–246, 2005. View at Google Scholar
  41. S. Massberg, I. Konrad, K. Schurzinger et al., “Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo,” The Journal of Experimental Medicine, vol. 203, no. 5, pp. 1221–1233, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. E. Chavakis, A. Hain, M. Vinci et al., “High-mobility group box 1 activates integrin-dependent homing of endothelial progenitor cells,” Circulation Research, vol. 100, no. 2, pp. 204–212, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. E. Chavakis, A. Aicher, C. Heeschen et al., “Role of beta2-integrins for homing and neovascularization capacity of endothelial progenitor cells,” The Journal of Experimental Medicine, vol. 201, no. 1, pp. 63–72, 2005. View at Google Scholar
  44. T. Bombeli, B. R. Schwartz, and J. M. Harlan, “Adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent bridging mechanism and novel roles for endothelial intercellular adhesion molecule 1 (ICAM-1), alphavbeta3 integrin, and GPIbalpha,” The Journal of Experimental Medicine, vol. 187, no. 3, pp. 329–339, 1998. View at Google Scholar
  45. H. Jin, A. Aiyer, J. Su et al., “A homing mechanism for bone marrow-derived progenitor cell recruitment to the neovasculature,” The Journal of Clinical Investigation, vol. 116, no. 3, pp. 652–662, 2006. View at Google Scholar
  46. G. Qin, M. Ii, M. Silver et al., “Functional disruption of alpha4 integrin mobilizes bone marrow-derived endothelial progenitors and augments ischemic neovascularization,” The Journal of Experimental Medicine, vol. 203, no. 1, pp. 153–163, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. T. Asahara, T. Takahashi, H. Masuda et al., “VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells,” The EMBO Journal, vol. 18, no. 14, pp. 3964–3972, 1999. View at Publisher · View at Google Scholar · View at Scopus
  48. M. A. Dery, M. D. Michaud, and D. E. Richard, “Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators,” The International Journal of Biochemistry & Cell Biology, vol. 37, no. 3, pp. 535–540, 2005. View at Google Scholar
  49. A. Groger, A. Piatkowski, G. Grieb, T. P. Wolter, P. C. Fuchs, and N. Pallua, “The mobilisation of mononuclear cells and endothelial progenitor cells after burn injury in a porcine model,” Burns, vol. 36, no. 4, pp. 545–551, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. M. H. Langenberg, M. W. Nijkamp, J. M. Roodhart et al., “Liver surgery induces an immediate mobilization of progenitor cells in liver cancer patients: a potential role for G-CSF,” Cancer Biology & Therapy, vol. 9, no. 9, pp. 743–748, 2010. View at Google Scholar
  51. J. Wang, Y. Zhong, X. Ma et al., “Analyses of endothelial cells and endothelial progenitor cells released microvesicles by using microbead and Q-dot based nanoparticle tracking analysis,” Scientific Reports, vol. 6, article 24679, 2016. View at Publisher · View at Google Scholar · View at Scopus
  52. C. A. Agudelo, Y. Tachibana, A. F. Hurtado, T. Ose, H. Iida, and T. Yamaoka, “The use of magnetic resonance cell tracking to monitor endothelial progenitor cells in a rat hind limb ischemic model,” Biomaterials, vol. 33, no. 8, pp. 2439–2448, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Moubarik, B. Guillet, B. Youssef et al., “Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke,” Stem Cell Reviews, vol. 7, no. 1, pp. 208–220, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Aicher, W. Brenner, M. Zuhayra et al., “Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling,” Circulation, vol. 107, no. 16, pp. 2134–2139, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. X. Zhou, A. Nicoletti, R. Elhage, and G. K. Hansson, “Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice,” Circulation, vol. 102, no. 24, pp. 2919–2922, 2000. View at Google Scholar
  56. L. Jonasson, J. Holm, O. Skalli, G. Bondjers, and G. K. Hansson, “Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque,” Arteriosclerosis, vol. 6, no. 2, pp. 131–138, 1986. View at Google Scholar
  57. Q. Xu, “The impact of progenitor cells in atherosclerosis,” Nature Clinical Practice Cardiovascular Medicine, vol. 3, no. 2, pp. 94–101, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. K. Jujo, M. Ii, and D. W. Losordo, “Endothelial progenitor cells in neovascularization of infarcted myocardium,” Journal of Molecular and Cellular Cardiology, vol. 45, no. 4, pp. 530–544, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. H. Masuda and T. Asahara, “Post-natal endothelial progenitor cells for neovascularization in tissue regeneration,” Cardiovascular Research, vol. 58, no. 2, pp. 390–398, 2003. View at Google Scholar
  60. Q. Shi, S. Rafii, M. H. Wu et al., “Evidence for circulating bone marrow-derived endothelial cells,” Blood, vol. 92, no. 2, pp. 362–367, 1998. View at Google Scholar
  61. C. H. Hu, Z. M. Li, Z. M. Du et al., “Expanded human cord blood-derived endothelial progenitor cells salvage infarcted myocardium in rats with acute myocardial infarction,” Clinical and Experimental Pharmacology & Physiology, vol. 37, no. 5-6, pp. 551–556, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Morancho, F. Ma, V. Barcelo, D. Giralt, J. Montaner, and A. Rosell, “Impaired vascular remodeling after endothelial progenitor cell transplantation in MMP9-deficient mice suffering cortical cerebral ischemia,” Journal of Cerebral Blood Flow and Metabolism, vol. 35, no. 10, pp. 1547–1551, 2015. View at Publisher · View at Google Scholar · View at Scopus
  63. Y. F. Li, L. N. Ren, G. Guo et al., “Endothelial progenitor cells in ischemic stroke: an exploration from hypothesis to therapy,” Journal of Hematology & Oncology, vol. 8, p. 33, 2015. View at Publisher · View at Google Scholar · View at Scopus
  64. Y. Dai, M. Ashraf, S. Zuo et al., “Mobilized bone marrow progenitor cells serve as donors of cytoprotective genes for cardiac repair,” Journal of Molecular and Cellular Cardiology, vol. 44, no. 3, pp. 607–617, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. D. A. Ingram, L. E. Mead, D. B. Moore, W. Woodard, A. Fenoglio, and M. C. Yoder, “Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells,” Blood, vol. 105, no. 7, pp. 2783–2786, 2005. View at Publisher · View at Google Scholar · View at Scopus
  66. B. D. Kelly, S. F. Hackett, K. Hirota et al., “Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1,” Circulation Research, vol. 93, no. 11, pp. 1074–1081, 2003. View at Publisher · View at Google Scholar · View at Scopus
  67. C. Schmidt-Lucke, L. Rossig, S. Fichtlscherer 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, vol. 111, no. 22, pp. 2981–2987, 2005. View at Publisher · View at Google Scholar · View at Scopus
  68. J. M. Hill, G. Zalos, J. P. Halcox et al., “Circulating endothelial progenitor cells, vascular function, and cardiovascular risk,” The New England Journal of Medicine, vol. 348, no. 7, pp. 593–600, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Rehman, J. Li, C. M. Orschell, and K. L. March, “Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors,” Circulation, vol. 107, no. 8, pp. 1164–1169, 2003. View at Google Scholar
  70. M. C. Deregibus, V. Cantaluppi, R. Calogero et al., “Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA,” Blood, vol. 110, no. 7, pp. 2440–2448, 2007. View at Google Scholar
  71. X. Li, C. Jiang, and J. Zhao, “Human endothelial progenitor cells-derived exosomes accelerate cutaneous wound healing in diabetic rats by promoting endothelial function,” Journal of Diabetes and Its Complications, vol. 30, no. 6, pp. 986–992, 2016. View at Publisher · View at Google Scholar · View at Scopus
  72. E. H. Lo and G. A. Rosenberg, “The neurovascular unit in health and disease: introduction,” Stroke, vol. 40, Supplement 3, pp. S2–S3, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. A. Rosell, A. Morancho, M. Navarro-Sobrino et al., “Factors secreted by endothelial progenitor cells enhance neurorepair responses after cerebral ischemia in mice,” PLoS One, vol. 8, no. 9, article e73244, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Di Santo, S. Seiler, A. L. Fuchs, J. Staudigl, and H. R. Widmer, “The secretome of endothelial progenitor cells promotes brain endothelial cell activity through PI3-kinase and MAP-kinase,” PLoS One, vol. 9, no. 4, article e95731, 2014. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Navarro-Sobrino, M. Hernandez-Guillamon, I. Fernandez-Cadenas et al., “The angiogenic gene profile of circulating endothelial progenitor cells from ischemic stroke patients,” Vascular Cell, vol. 5, no. 1, p. 3, 2013. View at Publisher · View at Google Scholar · View at Scopus
  76. J. Imitola, K. Raddassi, K. I. Park 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,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 52, pp. 18117–18122, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. A. Schanzer, F. P. Wachs, D. Wilhelm et al., “Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor,” Brain Pathology, vol. 14, no. 3, pp. 237–248, 2004. View at Google Scholar
  78. Y. H. Zhao, B. Yuan, J. Chen et al., “Endothelial progenitor cells: therapeutic perspective for ischemic stroke,” CNS Neuroscience & Therapeutics, vol. 19, no. 2, pp. 67–75, 2013. View at Publisher · View at Google Scholar · View at Scopus
  79. T. M. Hansen, A. J. Moss, and N. P. Brindle, “Vascular endothelial growth factor and angiopoietins in neurovascular regeneration and protection following stroke,” Current Neurovascular Research, vol. 5, no. 4, pp. 236–245, 2008. View at Google Scholar
  80. J. Wang, Y. Chen, Y. Yang et al., “Endothelial progenitor cells and neural progenitor cells synergistically protect cerebral endothelial cells from hypoxia/reoxygenation-induced injury via activating the PI3K/Akt pathway,” Molecular Brain, vol. 9, p. 12, 2016. View at Publisher · View at Google Scholar · View at Scopus
  81. X. Y. He, Z. Z. Chen, Y. Q. Cai et al., “Expression of cytokines in rat brain with focal cerebral ischemia after grafting with bone marrow stromal cells and endothelial progenitor cells,” Cytotherapy, vol. 13, no. 1, pp. 46–53, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. Y. Y. Bai, X. G. Peng, L. S. Wang et al., “Bone marrow endothelial progenitor cell transplantation after ischemic stroke: an investigation into its possible mechanism,” CNS Neuroscience & Therapeutics, vol. 21, no. 11, pp. 877–886, 2015. View at Publisher · View at Google Scholar · View at Scopus
  83. M. Vasa, S. Fichtlscherer, A. Aicher et al., “Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease,” Circulation Research, vol. 89, no. 1, pp. E1–E7, 2001. View at Google Scholar
  84. C. Kalka, H. Masuda, T. Takahashi et al., “Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 7, pp. 3422–3427, 2000. View at Publisher · View at Google Scholar · View at Scopus
  85. S. Shintani, T. Murohara, H. Ikeda et al., “Mobilization of endothelial progenitor cells in patients with acute myocardial infarction,” Circulation, vol. 103, no. 23, pp. 2776–2779, 2001. View at Google Scholar
  86. A. M. Leone, S. Rutella, G. Bonanno et al., “Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function,” European Heart Journal, vol. 26, no. 12, pp. 1196–1204, 2005. View at Publisher · View at Google Scholar · View at Scopus
  87. W. Wojakowski, M. Tendera, A. Michalowska et al., “Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction,” Circulation, vol. 110, no. 20, pp. 3213–3220, 2004. View at Google Scholar
  88. M. Massa, V. Rosti, M. Ferrario et al., “Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction,” Blood, vol. 105, no. 1, pp. 199–206, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. T. He, L. A. Smith, S. Harrington, K. A. Nath, N. M. Caplice, and Z. S. Katusic, “Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries,” Stroke, vol. 35, no. 10, pp. 2378–2384, 2004. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Vasa, S. Fichtlscherer, K. Adler et al., “Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease,” Circulation, vol. 103, no. 24, pp. 2885–2890, 2001. View at Google Scholar
  91. T. Eizawa, U. Ikeda, Y. Murakami et al., “Decrease in circulating endothelial progenitor cells in patients with stable coronary artery disease,” Heart, vol. 90, no. 6, pp. 685-686, 2004. View at Google Scholar
  92. G. B. Adams, R. P. Martin, I. R. Alley et al., “Therapeutic targeting of a stem cell niche,” Nature Biotechnology, vol. 25, no. 2, pp. 238–243, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. L. L. Wang, D. Chen, J. Lee et al., “Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice,” PLoS One, vol. 9, no. 2, article e87284, 2014. View at Publisher · View at Google Scholar · View at Scopus
  94. M. Ohtsuka, H. Takano, Y. Zou et al., “Cytokine therapy prevents left ventricular remodeling and dysfunction after myocardial infarction through neovascularization,” The FASEB Journal, vol. 18, no. 7, pp. 851–853, 2004. View at Google Scholar
  95. B. E. Strauer, M. Brehm, T. Zeus et al., “Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans,” Circulation, vol. 106, no. 15, pp. 1913–1918, 2002. View at Google Scholar
  96. B. Assmus, V. Schachinger, C. Teupe et al., “Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI),” Circulation, vol. 106, no. 24, pp. 3009–3017, 2002. View at Google Scholar
  97. F. Fernandez-Aviles, J. A. San Roman, J. Garcia-Frade et al., “Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction,” Circulation Research, vol. 95, no. 7, pp. 742–748, 2004. View at Google Scholar
  98. V. Schachinger, B. Assmus, M. B. Britten et al., “Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI trial,” Journal of the American College of Cardiology, vol. 44, no. 8, pp. 1690–1699, 2004. View at Publisher · View at Google Scholar · View at Scopus
  99. D. M. Leistner, U. Fischer-Rasokat, J. Honold et al., “Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy,” Clinical Research in Cardiology, vol. 100, no. 10, pp. 925–934, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. K. C. Wollert, G. P. Meyer, J. Lotz et al., “Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial,” Lancet, vol. 364, no. 9429, pp. 141–148, 2004. View at Google Scholar
  101. J. Tongers and D. W. Losordo, “Frontiers in nephrology: the evolving therapeutic applications of endothelial progenitor cells,” Journal of the American Society of Nephrology, vol. 18, no. 11, pp. 2843–2852, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. E. Tateishi-Yuyama, H. Matsubara, T. Murohara et al., “Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial,” Lancet, vol. 360, no. 9331, pp. 427–435, 2002. View at Publisher · View at Google Scholar · View at Scopus
  103. H. K. Yip, L. T. Chang, W. N. Chang et al., “Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke,” Stroke, vol. 39, no. 1, pp. 69–74, 2008. View at Google Scholar
  104. T. Bogoslovsky, A. Chaudhry, L. Latour et al., “Endothelial progenitor cells correlate with lesion volume and growth in acute stroke,” Neurology, vol. 75, no. 23, pp. 2059–2062, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. U. Ghani, A. Shuaib, A. Salam et al., “Endothelial progenitor cells during cerebrovascular disease,” Stroke, vol. 36, no. 1, pp. 151–153, 2005. View at Publisher · View at Google Scholar · View at Scopus
  106. J. Marti-Fabregas, R. Delgado-Mederos, J. Crespo et al., “Circulating endothelial progenitor cells and the risk of vascular events after ischemic stroke,” PLoS One, vol. 10, no. 4, article e0124895, 2015. View at Publisher · View at Google Scholar · View at Scopus
  107. S. I. Savitz, V. Misra, M. Kasam et al., “Intravenous autologous bone marrow mononuclear cells for ischemic stroke,” Annals of Neurology, vol. 70, no. 1, pp. 59–69, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Machado-Pereira, T. Santos, L. Ferreira, L. Bernardino, and R. Ferreira, “Challenging the great vascular wall: can we envision a simple yet comprehensive therapy for stroke?” Journal of Tissue Engineering and Regenerative Medicine, 2017. View at Publisher · View at Google Scholar
  109. K. Chu, K. I. Park, S. T. Lee et al., “Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia,” Neuroscience Research, vol. 53, no. 4, pp. 384–390, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. M. Vendrame, J. Cassady, J. Newcomb et al., “Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume,” Stroke, vol. 35, no. 10, pp. 2390–2395, 2004. View at Publisher · View at Google Scholar · View at Scopus
  111. V. Darsalia, S. J. Allison, C. Cusulin et al., “Cell number and timing of transplantation determine survival of human neural stem cell grafts in stroke-damaged rat brain,” Journal of Cerebral Blood Flow and Metabolism, vol. 31, no. 1, pp. 235–242, 2011. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Schmidt and J. Minnerup, “Promoting recovery from ischemic stroke,” Expert Review of Neurotherapeutics, vol. 16, no. 2, pp. 173–186, 2016. View at Publisher · View at Google Scholar · View at Scopus
  113. V. Misra, M. M. Ritchie, L. L. Stone, W. C. Low, and V. Janardhan, “Stem cell therapy in ischemic stroke: role of IV and intra-arterial therapy,” Neurology, vol. 79, Supplement 1, no. 13, pp. S207–S212, 2012. View at Publisher · View at Google Scholar · View at Scopus
  114. S. I. Savitz, J. H. Dinsmore, L. R. Wechsler, D. M. Rosenbaum, and L. R. Caplan, “Cell therapy for stroke,” NeuroRx, vol. 1, no. 4, pp. 406–414, 2004. View at Publisher · View at Google Scholar · View at Scopus
  115. L. Li, Q. Jiang, G. Ding et al., “Effects of administration route on migration and distribution of neural progenitor cells transplanted into rats with focal cerebral ischemia, an MRI study,” Journal of Cerebral Blood Flow and Metabolism, vol. 30, no. 3, pp. 653–662, 2010. View at Publisher · View at Google Scholar · View at Scopus
  116. S. Singh, B. M. Wu, and J. C. Dunn, “Accelerating vascularization in polycaprolactone scaffolds by endothelial progenitor cells,” Tissue Engineering Part A, vol. 17, no. 13-14, pp. 1819–1830, 2011. View at Publisher · View at Google Scholar · View at Scopus
  117. Z. Zhou, S. Shi, M. Song et al., “Development of transgenic endothelial progenitor cell-seeded stents,” Journal of Biomedical Materials Research, Part A, vol. 91, no. 2, pp. 623–628, 2009. View at Publisher · View at Google Scholar · View at Scopus
  118. R. Blindt, F. Vogt, I. Astafieva et al., “A novel drug-eluting stent coated with an integrin-binding cyclic Arg-Gly-Asp peptide inhibits neointimal hyperplasia by recruiting endothelial progenitor cells,” Journal of the American College of Cardiology, vol. 47, no. 9, pp. 1786–1795, 2006. View at Publisher · View at Google Scholar · View at Scopus
  119. M. A. Beijk, M. Klomp, K. T. Koch et al., “One-year clinical outcome after provisional T-stenting for bifurcation lesions with the endothelial progenitor cell capturing stent compared with the bare-metal stent,” Atherosclerosis, vol. 213, no. 2, pp. 525–531, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. M. Klomp, M. A. Beijk, N. J. Verouden, J. G. Tijssen, R. J. de Winter, and TRIAS Investigators, “Design and rationale of the TRI-stent adjudication study (TRIAS) program,” American Heart Journal, vol. 158, no. 4, pp. 527–532, 2009, e521. View at Publisher · View at Google Scholar · View at Scopus
  121. M. Klomp, M. A. Beijk, P. Damman et al., “Three-year clinical follow-up of an unselected patient population treated with the genous endothelial progenitor cell capturing stent,” Journal of Interventional Cardiology, vol. 24, no. 5, pp. 442–449, 2011. View at Publisher · View at Google Scholar · View at Scopus
  122. C. Dedobbeleer, D. Blocklet, M. Toungouz et al., “Myocardial homing and coronary endothelial function after autologous blood CD34+ progenitor cells intracoronary injection in the chronic phase of myocardial infarction,” Journal of Cardiovascular Pharmacology, vol. 53, no. 6, pp. 480–485, 2009. View at Publisher · View at Google Scholar · View at Scopus
  123. M. Teraa, R. W. Sprengers, R. E. Schutgens et al., “Effect of repetitive intra-arterial infusion of bone marrow mononuclear cells in patients with no-option limb ischemia: the randomized, double-blind, placebo-controlled Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial,” Circulation, vol. 131, no. 10, pp. 851–860, 2015. View at Publisher · View at Google Scholar · View at Scopus
  124. G. Sufen, Y. Xianghong, C. Yongxia, and P. Qian, “bFGF and PDGF-BB have a synergistic effect on the proliferation, migration and VEGF release of endothelial progenitor cells,” Cell Biology International, vol. 35, no. 5, pp. 545–551, 2011. View at Publisher · View at Google Scholar · View at Scopus
  125. P. V. Peplow, “Influence of growth factors and cytokines on angiogenic function of endothelial progenitor cells: a review of in vitro human studies,” Growth Factors, vol. 32, no. 3-4, pp. 83–116, 2014. View at Publisher · View at Google Scholar · View at Scopus
  126. O. Jeon, K. C. Hwang, K. J. Yoo, and B. S. Kim, “Combined sustained delivery of basic fibroblast growth factor and administration of granulocyte colony-stimulating factor: synergistic effect on angiogenesis in mouse ischemic limbs,” Journal of Endovascular Therapy, vol. 13, no. 2, pp. 175–181, 2006. View at Publisher · View at Google Scholar · View at Scopus
  127. E. Barbu, E. Molnar, J. Tsibouklis, and D. C. Górecki, “The potential for nanoparticle-based drug delivery to the brain: overcoming the blood-brain barrier,” Expert Opinion on Drug Delivery, vol. 6, no. 6, pp. 553–565, 2009. View at Publisher · View at Google Scholar · View at Scopus
  128. M. Goldsmith, L. Abramovitz, and D. Peer, “Precision nanomedicine in neurodegenerative diseases,” ACS Nano, vol. 8, no. 3, pp. 1958–1965, 2014. View at Publisher · View at Google Scholar · View at Scopus
  129. J. Kreuter, “Influence of the surface properties on nanoparticle-mediated transport of drugs to the brain,” Journal of Nanoscience and Nanotechnology, vol. 4, no. 5, pp. 484–488, 2004. View at Google Scholar
  130. P. R. Lockman, R. J. Mumper, M. A. Khan, and D. D. Allen, “Nanoparticle technology for drug delivery across the blood-brain barrier,” Drug Development and Industrial Pharmacy, vol. 28, no. 1, pp. 1–13, 2002. View at Publisher · View at Google Scholar · View at Scopus
  131. J. Sun, C. Zhang, G. Liu et al., “A novel mouse CD133 binding-peptide screened by phage display inhibits cancer cell motility in vitro,” Clinical & Experimental Metastasis, vol. 29, no. 3, pp. 185–196, 2012. View at Publisher · View at Google Scholar · View at Scopus
  132. E. T. Goh, E. Wong, Y. Farhatnia, A. Tan, and A. M. Seifalian, “Accelerating in situ endothelialisation of cardiovascular bypass grafts,” International Journal of Molecular Sciences, vol. 16, no. 1, pp. 597–627, 2014. View at Publisher · View at Google Scholar · View at Scopus
  133. D. H. Kim, Y. K. Seo, T. Thambi et al., “Enhancing neurogenesis and angiogenesis with target delivery of stromal cell derived factor-1alpha using a dual ionic pH-sensitive copolymer,” Biomaterials, vol. 61, pp. 115–125, 2015. View at Publisher · View at Google Scholar · View at Scopus
  134. W. Hiesinger, J. M. Perez-Aguilar, P. Atluri et al., “Computational protein design to reengineer stromal cell-derived factor-1alpha generates an effective and translatable angiogenic polypeptide analog,” Circulation, vol. 124, Supplement 11, pp. S18–S26, 2011. View at Publisher · View at Google Scholar · View at Scopus
  135. L. Chen, F. Wu, W. H. Xia et al., “CXCR4 gene transfer contributes to in vivo reendothelialization capacity of endothelial progenitor cells,” Cardiovascular Research, vol. 88, no. 3, pp. 462–470, 2010. View at Publisher · View at Google Scholar · View at Scopus
  136. J. X. Yu, X. F. Huang, W. M. Lv et al., “Combination of stromal-derived factor-1alpha and vascular endothelial growth factor gene-modified endothelial progenitor cells is more effective for ischemic neovascularization,” Journal of Vascular Surgery, vol. 50, no. 3, pp. 608–616, 2009. View at Publisher · View at Google Scholar · View at Scopus
  137. S. Sen, J. Merchan, J. Dean et al., “Autologous transplantation of endothelial progenitor cells genetically modified by adeno-associated viral vector delivering insulin-like growth factor-1 gene after myocardial infarction,” Human Gene Therapy, vol. 21, no. 10, pp. 1327–1334, 2010. View at Publisher · View at Google Scholar · View at Scopus
  138. C. Kalka, H. Masuda, T. Takahashi et al., “Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects,” Circulation Research, vol. 86, no. 12, pp. 1198–1202, 2000. View at Google Scholar
  139. H. Iwaguro, J. Yamaguchi, C. Kalka et al., “Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration,” Circulation, vol. 105, no. 6, pp. 732–738, 2002. View at Google Scholar
  140. D. P. Griese, S. Achatz, C. A. Batzlsperger et al., “Vascular gene delivery of anticoagulants by transplantation of retrovirally-transduced endothelial progenitor cells,” Cardiovascular Research, vol. 58, no. 2, pp. 469–477, 2003. View at Google Scholar
  141. D. Kong, L. G. Melo, A. A. Mangi et al., “Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells,” Circulation, vol. 109, no. 14, pp. 1769–1775, 2004. View at Publisher · View at Google Scholar · View at Scopus
  142. L. Zhao, X. Liu, Y. Zhang et al., “Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction,” Experimental Cell Research, vol. 344, no. 1, pp. 30–39, 2016. View at Publisher · View at Google Scholar · View at Scopus
  143. M. S. Khubutiya, A. V. Vagabov, A. A. Temnov, and A. N. Sklifas, “Paracrine mechanisms of proliferative, anti-apoptotic and anti-inflammatory effects of mesenchymal stromal cells in models of acute organ injury,” Cytotherapy, vol. 16, no. 5, pp. 579–585, 2014. View at Publisher · View at Google Scholar · View at Scopus
  144. A. J. Man, G. Kujawski, T. S. Burns et al., “Neurogenic potential of engineered mesenchymal stem cells overexpressing VEGF,” Cellular and Molecular Bioengineering, vol. 9, no. 1, pp. 96–106, 2016. View at Publisher · View at Google Scholar · View at Scopus
  145. J. Ben-Shoshan and J. George, “Endothelial progenitor cells as therapeutic vectors in cardiovascular disorders: from experimental models to human trials,” Pharmacology & Therapeutics, vol. 115, no. 1, pp. 25–36, 2007. View at Publisher · View at Google Scholar · View at Scopus
  146. T. Akita, T. Murohara, H. Ikeda et al., “Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization,” Laboratory Investigation, vol. 83, no. 1, pp. 65–73, 2003. View at Google Scholar
  147. S. P. Yu, Z. Wei, and L. Wei, “Preconditioning strategy in stem cell transplantation therapy,” Translational Stroke Research, vol. 4, no. 1, pp. 76–88, 2013. View at Publisher · View at Google Scholar · View at Scopus
  148. F. Zemani, J. S. Silvestre, F. Fauvel-Lafeve et al., “Ex vivo priming of endothelial progenitor cells with SDF-1 before transplantation could increase their proangiogenic potential,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 4, pp. 644–650, 2008. View at Publisher · View at Google Scholar · View at Scopus
  149. F. M. Rauscher, P. J. Goldschmidt-Clermont, B. H. Davis et al., “Aging, progenitor cell exhaustion, and atherosclerosis,” Circulation, vol. 108, no. 4, pp. 457–463, 2003. View at Google Scholar
  150. D. J. Nolan, A. Ciarrocchi, A. S. Mellick et al., “Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization,” Genes & Development, vol. 21, no. 12, pp. 1546–1558, 2007. View at Publisher · View at Google Scholar · View at Scopus
  151. J. Hur, C. H. Yoon, H. S. Kim et al., “Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 2, pp. 288–293, 2004. View at Publisher · View at Google Scholar · View at Scopus
  152. B. W. van der Strate, E. R. Popa, M. Schipper et al., “Circulating human CD34+ progenitor cells modulate neovascularization and inflammation in a nude mouse model,” Journal of Molecular and Cellular Cardiology, vol. 42, no. 6, pp. 1086–1097, 2007. View at Publisher · View at Google Scholar · View at Scopus
  153. M. Slevin, P. Kumar, J. Gaffney, S. Kumar, and J. Krupinski, “Can angiogenesis be exploited to improve stroke outcome? Mechanisms and therapeutic potential,” Clinical Science (London, England), vol. 111, no. 3, pp. 171–183, 2006. View at Publisher · View at Google Scholar · View at Scopus
  154. D. C. Ding, C. H. Lin, W. C. Shyu, and S. Z. Lin, “Neural stem cells and stroke,” Cell Transplantation, vol. 22, no. 4, pp. 619–630, 2013. View at Google Scholar
  155. J. K. Strecker, J. Olk, M. Hoppen et al., “Combining growth factor and bone marrow cell therapy induces bleeding and alters immune response after stroke in mice,” Stroke, vol. 47, no. 3, pp. 852–862, 2016. View at Publisher · View at Google Scholar · View at Scopus