About this Journal Submit a Manuscript Table of Contents
Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 871272, 10 pages
http://dx.doi.org/10.1155/2012/871272
Review Article

Role of Pigment Epithelium-Derived Factor in Stem/Progenitor Cell-Associated Neovascularization

1Department of Neurosurgery, School of Medicine, Chung-Shan Medical University and Hospital, Taichung 402, Taiwan
2Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
3Graduate Institutes of Integrated Medicine and Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan
4Departments of Urology, Obstetrics and Gynecology, and Medical Research, China Medical University Hospital, Taichung 404, Taiwan
5Department of Anesthesiology, Tungs’ Taichung Metroharbor Hospital, Taichung 433, Taiwan
6Department of Fragrance and Cosmetic Science, and Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
7School of Medicine, Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan

Received 12 December 2011; Accepted 26 March 2012

Academic Editor: Crispin Dass

Copyright © 2012 Jung-Tung Liu 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. J. Tombran-Tink and L. V. Johnson, “Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells,” Investigative Ophthalmology and Visual Science, vol. 30, no. 8, pp. 1700–1707, 1989. View at Scopus
  2. F. R. Steele, G. J. Chader, L. V. Johnson, and J. Tombran-Tink, “Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 4, pp. 1526–1530, 1993. View at Publisher · View at Google Scholar · View at Scopus
  3. E. T. H. Ek, C. R. Dass, and P. F. M. Choong, “PEDF: a potential molecular therapeutic target with multiple anti-cancer activities,” Trends in Molecular Medicine, vol. 12, no. 10, pp. 497–502, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. K. Rychli, K. Huber, and J. Wojta, “Pigment epithelium-derived factor (PEDF) as a therapeutic target in cardiovascular disease,” Expert Opinion on Therapeutic Targets, vol. 13, no. 11, pp. 1295–1302, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. J. Tombran-Tink, G. G. Chader, and L. V. Johnson, “PEDF: a pigment epithelium-derived factor with potent neuronal differentiative activity[2],” Experimental Eye Research, vol. 53, no. 3, pp. 411–414, 1991. View at Publisher · View at Google Scholar · View at Scopus
  6. M. M. Bilak, A. M. Corse, S. R. Bilak, M. Lehar, J. Tombran-Tink, and R. W. Kuncl, “Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration,” Journal of Neuropathology and Experimental Neurology, vol. 58, no. 7, pp. 719–728, 1999. View at Scopus
  7. M. A. DeCoster, E. Schabelman, J. Tombran-Tink, et al., “Neuroprotection by pigment epithelial-derived factor against glutamate toxicity in developing primary hippocampal neurons,” Journal of Neuroscience Research, vol. 56, no. 6, pp. 604–610, 1999.
  8. T. Falk, S. Zhang, and S. J. Sherman, “Pigment epithelium derived factor (PEDF) is neuroprotective in two in vitro models of Parkinson's disease,” Neuroscience Letters, vol. 458, no. 2, pp. 49–52, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Sanagi, T. Yabe, and H. Yamada, “Adenoviral gene delivery of pigment epithelium-derived factor protects striatal neurons from quinolinic acid-induced excitotoxicity,” Journal of Neuropathology and Experimental Neurology, vol. 69, no. 3, pp. 224–233, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. D. W. Dawson, O. V. Volpert, P. Gillis et al., “Pigment epithelium-derived factor: a potent inhibitor of angiogenesis,” Science, vol. 285, no. 5425, pp. 245–248, 1999. View at Publisher · View at Google Scholar · View at Scopus
  11. E. M. Levy, M. P. Roberti, and J. Mordoh, “Natural killer cells in human cancer: from biological functions to clinical applications,” Journal of Biomedicine and Biotechnology, vol. 2011, Article ID 676198, 11 pages, 2011. View at Publisher · View at Google Scholar
  12. S. X. Zhang, J. J. Wang, G. Gao, C. Shao, R. Mott, and J. X. Ma, “Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor,” FASEB Journal, vol. 20, no. 2, pp. 323–325, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. S. I. Yamagishi, K. Nakamura, S. Ueda, S. Kato, and T. Imaizumi, “Pigment epithelium-derived factor (PEDF) blocks angiotensin II signaling in endothelial cells via suppression of NADPH oxidase: a novel anti-oxidative mechanism of PEDF,” Cell and Tissue Research, vol. 320, no. 3, pp. 437–445, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. S. H. Wang, S. J. Lin, Y. H. Chen et al., “Late outgrowth endothelial cells derived from wharton jelly in human umbilical cord reduce neointimal formation after vascular injury: involvement of pigment epithelium-derived factor,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 6, pp. 816–822, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Tombran-Tink, “PEDF in angiogenic eye diseases,” Current Molecular Medicine, vol. 10, no. 3, pp. 267–278, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. H. Funatsu, H. Yamashita, S. Nakamura et al., “Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor are related to diabetic macular edema,” Ophthalmology, vol. 113, no. 2, pp. 294–301, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. J. A. Doll, V. M. Stellmach, N. P. Bouck et al., “Pigment epithelium-derived factor regulates the vasculature and mass of the prostate and pancreas,” Nature Medicine, vol. 9, no. 6, pp. 774–780, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Hase, M. Miyamoto, H. Uehara et al., “Pigment epithelium-derived factor gene therapy inhibits human pancreatic cancer in mice,” Clinical Cancer Research, vol. 11, no. 24, pp. 8737–8744, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Filleur, K. Volz, T. Nelius et al., “Two functional epitopes of pigment epithelial-derived factor block angiogenesis and induce differentiation in prostate cancer,” Cancer Research, vol. 65, no. 12, pp. 5144–5152, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. R. Abe, Y. Fujita, S. I. Yamagishi, and H. Shimizu, “Pigment epithelium-derived factor prevents melanoma growth via angiogenesis inhibition,” Current Pharmaceutical Design, vol. 14, no. 36, pp. 3802–3809, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. A. L. George, P. Bangalore-Prakash, S. Rajoria et al., “Endothelial progenitor cell biology in disease and tissue regeneration,” Journal of Hematology and Oncology, vol. 4, article 24, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Matthias, N. David, and N. Josef, “From bench to bedside: what physicians need to know about endothelial progenitor cells,” American Journal of Medicine, vol. 124, no. 6, pp. 489–497, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. A. J. Roks, K. Rodgers, and T. Walther, “Effects of the renin angiotensin system on vasculogenesis-related progenitor cells,” Current Opinion in Pharmacology, vol. 11, no. 2, pp. 162–174, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. S. Fang and P. Salven, “Stem cells in tumor angiogenesis,” Journal of Molecular and Cellular Cardiology, vol. 50, no. 2, pp. 290–295, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. R. Longeras, K. Farjo, M. Ihnat, et al., “A PEDF-derived peptide inhibits retinal neovascularization and blocks mobilization of bone marrow-derived endothelial progenitor cells,” Experimental Diabetes Research, vol. 2012, Article ID 518426, 11 pages, 2012. View at Publisher · View at Google Scholar
  26. W. D. Thompson, W. W. Li, and M. Maragoudakis, “The clinical manipulation of angiogenesis: pathology, side-effects, surprises, and opportunities with novel human therapies,” The Journal of Pathology, vol. 190, no. 3, pp. 330–337, 2000.
  27. J. M. Isner and T. Asahara, “Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization,” Journal of Clinical Investigation, vol. 103, no. 9, pp. 1231–1236, 1999. View at Scopus
  28. S. Patel-Hett and P. A. D'Amore, “Signal transduction in vasculogenesis and developmental angiogenesis,” International Journal of Developmental Biology, vol. 55, no. 4-5, pp. 353–369, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. 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
  30. J. Lu, V. J. Pompili, and H. Das, “Neovascularization and hematopoietic stem cells,” Cell Biochemistry and Biophysics. In press.
  31. M. B. Grant, W. S. May, S. Caballero et al., “Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization,” Nature Medicine, vol. 8, no. 6, pp. 607–612, 2002. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Rafii and D. Lyden, “Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration,” Nature Medicine, vol. 9, no. 6, pp. 702–712, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. I. Rajantie, M. Ilmonen, A. Alminaite, U. Ozerdem, K. Alitalo, and P. Salven, “Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells,” Blood, vol. 104, no. 7, pp. 2084–2086, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. B. A. Peters, L. A. Diaz, K. Polyak et al., “Contribution of bone marrow-derived endothelial cells to human tumor vasculature,” Nature Medicine, vol. 11, no. 3, pp. 261–262, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Napoli, T. Hayashi, F. Cacciatore et al., “Endothelial progenitor cells as therapeutic agents in the microcirculation: an update,” Atherosclerosis, vol. 215, no. 1, pp. 9–22, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. 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 Publisher · View at Google Scholar · View at Scopus
  37. T. Ziegelhoeffer, B. Fernandez, S. Kostin et al., “Bone marrow-derived cells do not incorporate into the adult growing vasculature,” Circulation Research, vol. 94, no. 2, pp. 230–238, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. 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
  39. 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
  40. Y. H. Chen, S. J. Lin, F. Y. Lin et al., “High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms,” Diabetes, vol. 56, no. 6, pp. 1559–1568, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. T. Asahara, H. Masuda, T. Takahashi et al., “Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization,” Circulation Research, vol. 85, no. 3, pp. 221–228, 1999. View at Scopus
  42. M. Ii, H. Nishimura, A. Iwakura et al., “Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via “imported” nitric oxide synthase activity,” Circulation, vol. 111, no. 9, pp. 1114–1120, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. S. M. Bauer, L. J. Goldstein, R. J. Bauer, H. Chen, M. Putt, and O. C. Velazquez, “The bone marrow-derived endothelial progenitor cell response is impaired in delayed wound healing from ischemia,” Journal of Vascular Surgery, vol. 43, no. 1, pp. 134–141, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. H. Masuda, C. Kalka, T. Takahashi et al., “Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis,” Circulation Research, vol. 101, no. 6, pp. 598–606, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. T. Murayama, O. M. Tepper, M. Silver et al., “Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo,” Experimental Hematology, vol. 30, no. 8, pp. 967–972, 2002. View at Publisher · View at Google Scholar · View at Scopus
  46. N. I. Moldovan and T. Asahara, “Role of blood mononuclear cells in recanalization and vascularization of thrombi: past, present, and future,” Trends in Cardiovascular Medicine, vol. 13, no. 7, pp. 265–269, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Folkman and Y. Shing, “Angiogenesis,” Journal of Biological Chemistry, vol. 267, no. 16, pp. 10931–10934, 1992. View at Scopus
  48. 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
  49. T. Asahara, A. Kawamoto, and H. Masuda, “Concise review: circulating endothelial progenitor cells for vascular medicine,” Stem Cells, vol. 29, no. 11, pp. 1650–1655, 2011.
  50. S. Arnhold, P. Heiduschka, H. Klein et al., “Adenovirally transduced bone marrow stromal cells differentiate into pigment epithelial cells and induce rescue effects in RCS rats,” Investigative Ophthalmology and Visual Science, vol. 47, no. 9, pp. 4121–4129, 2006. View at Publisher · View at Google Scholar · View at Scopus
  51. M. O. Karl and T. A. Reh, “Regenerative medicine for retinal diseases: activating endogenous repair mechanisms,” Trends in Molecular Medicine, vol. 16, no. 4, pp. 193–202, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. F. Gaillard and Y. Sauvé, “Cell-based therapy for retina degeneration: the promise of a cure,” Vision Research, vol. 47, no. 22, pp. 2815–2824, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Caputo, H. Zirpoli, R. Di Benedetto, K. De Nadai, and M. F. Tecce, “Perspectives of choroidal neovascularization therapy,” Current Drug Targets, vol. 12, no. 2, pp. 234–242, 2011. View at Scopus
  54. T. Chan-Ling, J. E. Dahlstrom, M. E. Koina et al., “Evidence of hematopoietic differentiation, vasculogenesis and angiogenesis in the formation of human choroidal blood vessels,” Experimental Eye Research, vol. 92, no. 5, pp. 361–376, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. H. Y. Hou, H. L. Liang, Y. S. Wang et al., “A therapeutic strategy for choroidal neovascularization based on recruitment of mesenchymal stem cells to the sites of lesions,” Molecular Therapy, vol. 18, no. 10, pp. 1837–1845, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. A. De Marzo, C. Aruta, and V. Marigo, “PEDF promotes retinal neurosphere formation and expansion in vitro,” Advances in Experimental Medicine and Biology, vol. 664, pp. 621–630, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. C. Aruta, F. Giordano, A. De Marzo et al., “In vitro differentiation of retinal pigment epithelium from adult retinal stem cells,” Pigment Cell and Melanoma Research, vol. 24, no. 1, pp. 233–240, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. D. Zhu, X. Deng, C. Spee et al., “Polarized secretion of PEDF from human embryonic stem cell-derived RPE promotes retinal progenitor cell survival,” Investigative Ophthalmology and Visual Science, vol. 52, no. 3, pp. 1573–1585, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. H. Vaajasaari, T. Ilmarinen, K. Juuti-Uusitalo et al., “Toward the defined and xeno-free differentiation of functional human pluripotent stem cell-derived retinal pigment epithelial cells,” Molecular Vision, vol. 17, pp. 558–575, 2011. View at Scopus
  60. S. I. Yamagishi, T. Matsui, K. Nakamura, S. Ueda, Y. Noda, and T. Imaizumi, “Pigment epithelium-derived factor (PEDF): its potential therapeutic implication in diabetic vascular complications,” Current drug targets, vol. 9, no. 11, pp. 1025–1029, 2008. View at Scopus
  61. C. H. Chang, C. S. Tsai, Y. F. Jim, H. C. Wu, C. C. Lin, and A. Kao, “Lumbar bone mineral density in prostate cancer patients with bone metastases,” Endocrine Research, vol. 29, no. 2, pp. 177–182, 2003. View at Publisher · View at Google Scholar · View at Scopus
  62. Y. Zhao, Q. Bao, A. Renner et al., “Cancer stem cells and angiogenesis,” International Journal of Developmental Biology, vol. 55, no. 4-5, pp. 477–482, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. X. H. Yao, Y. F. Ping, and X. W. Bian, “Contribution of cancer stem cells to tumor vasculogenic mimicry,” Protein and Cell, vol. 2, no. 4, pp. 266–272, 2011.
  64. W. Fan, R. Crawford, and Y. Xiao, “The ratio of VEGF/PEDF expression in bone marrow mesenchymal stem cells regulates neovascularization,” Differentiation, vol. 81, no. 3, pp. 181–191, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. K. B. Manalo, P. F. Choong, and C. R. Dass, “Pigment epithelium-derived factor as an impending therapeutic agent against vascular epithelial growth factor-driven tumor-angiogenesis,” Molecular Carcinogenesis, vol. 50, no. 2, pp. 67–72, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. L. Elzaouk, K. Moelling, and J. Pavlovic, “Anti-tumor activity of mesenchymal stem cells producing IL-12 in a mouse melanoma model,” Experimental Dermatology, vol. 15, no. 11, pp. 865–874, 2006. View at Publisher · View at Google Scholar · View at Scopus
  67. P. Gao, Q. Ding, Z. Wu, H. Jiang, and Z. Fang, “Therapeutic potential of human mesenchymal stem cells producing IL-12 in a mouse xenograft model of renal cell carcinoma,” Cancer Letters, vol. 290, no. 2, pp. 157–166, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. D. P. Fitzgerald, P. Subramanian, M. Deshpande, et al., “Opposing effects of pigment epithelium-derived factor on breast cancer cell versus neuronal survival: implication for brain metastasis and metastasis-induced brain damage,” Cancer Research, vol. 72, no. 1, pp. 144–153, 2012.
  69. Y. Gao, A. Yao, W. Zhang et al., “Human mesenchymal stem cells overexpressing pigment epithelium-derived factor inhibit hepatocellular carcinoma in nude mice,” Oncogene, vol. 29, no. 19, pp. 2784–2794, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. Y. F. Ping and X. W. Bian, “Consice review: contribution of cancer stem cells to neovascularization,” Stem Cells, vol. 29, no. 6, pp. 888–894, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. L. Z. Zhang, C. Q. Zhang, Z. Y. Yan, Q. C. Yang, Y. Jiang, and B. F. Zeng, “Tumor-initiating cells and tumor vascularization,” Pediatric Blood and Cancer, vol. 56, no. 3, pp. 335–340, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. J. W. Chen, Y. H. Chen, and S. J. Lin, “Long-term exposure to oxidized low-density lipoprotein enhances tumor necrosis factor-α-stimulated endothelial adhesiveness of monocytes by activating superoxide generation and redox-sensitive pathways,” Free Radical Biology and Medicine, vol. 40, no. 5, pp. 817–826, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. C. S. Tsai, F. Y. Lin, Y. H. Chen et al., “Cilostazol attenuates MCP-1 and MMP-9 expression in vivo in LPS-administrated balloon-injured rabbit aorta and in vitro in LPS-treated monocytic THP-1 cells,” Journal of Cellular Biochemistry, vol. 103, no. 1, pp. 54–66, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. Y. H. Chen, S. J. Lin, Y. L. Chen, P. L. Liu, and J. W. Chen, “Anti-inflammatory effects of different drugs/agents with antioxidant property on endothelial expression of adhesion molecules,” Cardiovascular and Hematological Disorders, vol. 6, no. 4, pp. 279–304, 2006. View at Scopus
  75. C. H. Wu, B. R. Tsai, W. T. Hsieh, G. Y. Chang, S. J. T. Mao, and W. C. Chang, “The preventive effects of G115 on balloon injury-induced neointima formation in rats,” Life Sciences, vol. 70, no. 6, pp. 669–679, 2001. View at Publisher · View at Google Scholar · View at Scopus
  76. H. C. Huang, G. Y. Shi, S. J. Jiang et al., “Thrombomodulin-mediated cell adhesion: involvement of its lectin-like domain,” Journal of Biological Chemistry, vol. 278, no. 47, pp. 46750–46759, 2003. View at Publisher · View at Google Scholar · View at Scopus
  77. M. Peichev, A. J. Naiyer, D. Pereira et al., “Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors,” Blood, vol. 95, no. 3, pp. 952–958, 2000. View at Scopus
  78. R. K. Burt, Y. Loh, W. Pearce et al., “Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases,” Journal of the American Medical Association, vol. 299, no. 8, pp. 925–936, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. E. Crimi, L. J. Ignarro, and C. Napoli, “Microcirculation and oxidative stress,” Free Radical Research, vol. 41, no. 12, pp. 1364–1375, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. R. Karra, S. Vemullapalli, C. Dong et al., “Molecular evidence for arterial repair in atherosclerosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 46, pp. 16789–16794, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. C. Napoli, C. Maione, C. Schiano, C. Fiorito, and L. J. Ignarro, “Bone marrow cell-mediated cardiovascular repair: potential of combined therapies,” Trends in Molecular Medicine, vol. 13, no. 7, pp. 278–286, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. K. Nakamura, S. I. Yamagishi, T. Matsui et al., “Pigment epithelium-derived factor inhibits neointimal hyperplasia after vascular injury by blocking NADPH oxidase-mediated reactive oxygen species generation,” American Journal of Pathology, vol. 170, no. 6, pp. 2159–2170, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. S. I. Yamagishi, Y. Inagaki, K. Nakamura et al., “Pigment epithelium-derived factor inhibits TNF-α-induced interleukin-6 expression in endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation,” Journal of Molecular and Cellular Cardiology, vol. 37, no. 2, pp. 497–506, 2004. View at Publisher · View at Google Scholar · View at Scopus
  84. S. T. Kao, C. C. Yeh, C. C. Hsieh et al., “The Chinese medicine Bu-Zhong-Yi-Qi-Tang inhibited proliferation of hepatoma cell lines by inducing apoptosis via G0/G1 arrest,” Life Sciences, vol. 69, no. 13, pp. 1485–1496, 2001. View at Publisher · View at Google Scholar · View at Scopus
  85. S. H. Fang, Y. C. Hou, W. C. Chang, S. L. Hsiu, P. D. L. Chao, and B. L. Chiang, “Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock,” Life Sciences, vol. 74, no. 6, pp. 743–756, 2003. View at Publisher · View at Google Scholar · View at Scopus
  86. H. Liang, H. Hou, W. Yi, et al., “Increased expression of pigment epithelium-derived factor in aged mesenchymal stem cells impairs their therapeutic efficacy for attenuating myocardial infarction injury,” European Heart Journal. In press.
  87. N. L. Ward and J. C. LaManna, “The neurovascular unit and its growth factors: coordinated response in the vascular and nervous systems,” Neurological Research, vol. 26, no. 8, pp. 870–883, 2004. View at Publisher · View at Google Scholar · View at Scopus
  88. Q. Shen, S. K. Goderie, L. Jin et al., “Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells,” Science, vol. 304, no. 5675, pp. 1338–1340, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. K. Pumiglia and S. Temple, “PEDF: bridging neurovascular interactions in the stem cell niche,” Nature Neuroscience, vol. 9, no. 3, pp. 299–300, 2006. View at Publisher · View at Google Scholar · View at Scopus
  90. C. Ramírez-Castillejo, F. Sánchez-Sánchez, C. Andreu-Agulló et al., “Pigment epithelium-derived factor is a niche signal for neural stem cell renewal,” Nature Neuroscience, vol. 9, no. 3, pp. 331–339, 2006. View at Publisher · View at Google Scholar · View at Scopus
  91. D. Palmieri, J. M. Watson, and C. A. Rinehart, “Age-related expression of PEDF/EPC-1 in human endometrial stromal fibroblasts: implications for interactive senescence,” Experimental Cell Research, vol. 247, no. 1, pp. 142–147, 1999. View at Publisher · View at Google Scholar · View at Scopus
  92. M. Tavazoie, L. Van der Veken, V. Silva-Vargas et al., “A specialized vascular niche for adult neural stem cells,” Cell Stem Cell, vol. 3, no. 3, pp. 279–288, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. Q. Shen, Y. Wang, E. Kokovay et al., “Adult SVZ stem cells lie in a vascular Niche: a quantitative analysis of Niche cell-cell interactions,” Cell Stem Cell, vol. 3, no. 3, pp. 289–300, 2008. View at Publisher · View at Google Scholar · View at Scopus
  94. C. Andreu-Agullo, J. M. Morante-Redolat, A. C. Delgado, et al., “Vascular niche factor PEDF modulates notch-dependent stemness in the adult subependymal zone,” Nature Neuroscience, vol. 12, no. 12, pp. 1514–1523, 2009. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Filleur, T. Nelius, W. De Riese, and R. C. Kennedy, “Characterization of pedf: a multi-functional serpin family protein,” Journal of Cellular Biochemistry, vol. 106, no. 5, pp. 769–775, 2009. View at Publisher · View at Google Scholar · View at Scopus