Morphology and Properties of Pericytes

  • Paula Dore-DuffyEmail author
  • Kristen Cleary
Part of the Methods in Molecular Biology book series (MIMB, volume 686)


Pericytes were described in 1873 by the French scientist Charles-Marie Benjamin Rouget and were originally called Rouget cells. The Rouget cell was renamed some years later due to its anatomical location abluminal to the endothelial cell (EC) and luminal to parenchymal cells. In the brain, pericytes are located in precapillary arterioles, capillaries and postcapillary venules. They deposit elements of the basal lamina and are totally surrounded by this vascular component. Pericytes are important cellular constituents of the blood–brain barrier (BBB) and actively communicate with other cells of the neurovascular unit such as ECs, astrocytes, and neurons. Pericytes are local regulatory cells that are important for the maintenance of homeostasis and hemostasis, and are a source of adult pluripotent stem cells. Further understanding of the role played by this intriguing cell may lead to novel targeted therapies for neurovascular diseases.

Key words

Angiogenesis Blood–brain barrier Capillaries Contractility DNA repair Endothelial cells Gap junction Homeostasis Migration Neurovascular unit Pericyte Stem cells Stress response Vascular injury 



The work discussed in this manuscript was supported by grants from the National Institutes of Health and the National Multiple Sclerosis Society.


  1. 1.
    Rouget, C. (1874) Note sur le developpement de la tunique contractile des vaisseaux Compt Rend Acad Sci 59, 559–562.Google Scholar
  2. 2.
    Doré, SE. (1923) On the contractility and nervous supply of the capillaries Brit J Derma 35, 398–404.CrossRefGoogle Scholar
  3. 3.
    Blood, D. C., and Studdert, V.P. (1988) Baillière’s Comprehensive Veterinary Dictionary, Baillère Tindall, London.Google Scholar
  4. 4.
    Stedman, T. L. (1995) Stedman’s Medical Dictionary, Williams & Wilkins, Baltimore.Google Scholar
  5. 5.
    Fabry, Z., Fitzsimmons, K. M., Herlein, J. A., Moninger, T. O., Dobbs, M. B., and Hart, M. N. (1993) Production of the cytokines interleukin 1 and 6 by murine brain microvessel endothelium and smooth muscle pericytes J Neuroimmunol 47, 23–34.PubMedCrossRefGoogle Scholar
  6. 6.
    Ding, R., Darland, D.C., Parmacek, M.S., and D’Amore, P.A. (2004) Endothelial-mesenchymal interactions in vitro reveal molecular mechanisms of smooth muscle/pericyte differentiation Stem Cells Dev 13, 509–520.PubMedGoogle Scholar
  7. 7.
    Pericytes [online]. [last accessed 2009 Jan 09]. Available from:
  8. 8.
    Balabanov, R. and Dore-Duffy, P. (1998) Role of the CNS microvascular pericyte in the blood-brain barrier J Neurosci Res 53, 637–644.PubMedCrossRefGoogle Scholar
  9. 9.
    Dore-Duffy, P., Katychev, A., Wang, X., and Van Buren, E. (2006) CNS microvascular pericytes exhibit multipotential stem cell activity J Cereb Blood Flow Metab 26, 613–624.PubMedCrossRefGoogle Scholar
  10. 10.
    Krüger, M., and Bechmann, I. (2008) Pericytes, in Central Nervous System Diseases and Inflammation (Lane, T. E., Bergmann, C., Carson, M., Wyss-Coray, T., Ed.), pp 33–43, Springer, Berlin.CrossRefGoogle Scholar
  11. 11.
    Sims, D.E. (1991) Recent advances in pericyte biology–implications for health and disease Can J Cardiol 7, 431–443.PubMedGoogle Scholar
  12. 12.
    Tilton, R.G. (1991) Capillary pericytes: perspectives and future trends J Electron Microsc Tech 19, 327-344.PubMedCrossRefGoogle Scholar
  13. 13.
    Shepro, D., and Morel, N.M. (1993) Pericyte physiology FASEB J 7, 1031–1038.PubMedGoogle Scholar
  14. 14.
    Dore-Duffy, P. (2008) Pericytes: Pluripotent cells of the blood brain barrier Curr Pharm Des 14, 1581–1593.PubMedCrossRefGoogle Scholar
  15. 15.
    Dore-Duffy, P. (2003) Isolation and characterization of cerebral microvascular pericytes Methods Mol Med 89, 375-82.PubMedGoogle Scholar
  16. 16.
    Du, R., Petritsch, C., Lu, K., Liu, P., Haller, A., Ganss, R., Song, H., Vandenberg, S., and Bergers, G. (2008) Matrix metalloproteinase-2 regulates vascular patterning and growth affecting tumor cell survival and invasion in GBM Neuro Oncol 10, 254–264.PubMedCrossRefGoogle Scholar
  17. 17.
    Gonul, E., Duz, B., Kahraman, S., Kayali, H., Kubar, A., and Timurkaynak, E. (2002) Early pericyte response to brain hypoxia in cats: an ultrastructural study Microvasc Res 64, 116–119.PubMedCrossRefGoogle Scholar
  18. 18.
    Arismendi-Morillo, G., and Castellano, A. (2005) Tumoral micro-blood vessels and vascular microenvironment in human astrocytic tumors. A transmission electron microscopy study J Neurooncol 73, 211–217.PubMedCrossRefGoogle Scholar
  19. 19.
    Wiley, L.A., Rupp, G.R., and Steinle, J.J. (2005) Sympathetic innervation regulates basement membrane thickening and pericyte number in rat retina Invest Ophthalmol Vis Sci 46, 744–748.PubMedCrossRefGoogle Scholar
  20. 20.
    Hughes, S. J., Wall, N., Scholfield, C. N., McGeown, J. G., Gardiner, T. A., Stitt, A. W., and Curtis, T. M. (2004) Advanced glycation endproduct modified basement membrane attenuates endothelin-1 induced [Ca2+]i signalling and contraction in retinal microvascular pericytes, Mol Vis 10, 996–1004.PubMedGoogle Scholar
  21. 21.
    Dore-Duffy, P., Owen, C., Balabanov, R., Murphy, S., Beaumont, T., and Rafols, J.A. (2000) Pericyte migration from the vascular wall in response to traumatic brain injury Microvasc Res 60, 55–69.PubMedCrossRefGoogle Scholar
  22. 22.
    McCarty, J.H., Monahan-Earley, R.A., Brown, L.F., Keller, M., Gerhardt,H., Rubin, K., Shani, M., Dvorak, H.F., Wolburg, H., Bader, B.L., Dvorak, A.M., and Hynes, R.O. (2002) Defective associations between blood vessels and brain parenchyma lead to cerebral hemorrhage in mice lacking alphav integrins Mol Cell Biol 22, 7667–7677.PubMedCrossRefGoogle Scholar
  23. 23.
    McCarty, J.H. (2005) Cell biology of the neurovascular unit: implications for drug delivery across the blood-brain barrier Assay Drug Dev Technol 3, 89–95.PubMedCrossRefGoogle Scholar
  24. 24.
    Hayden, M.R., Sowers, J.R., and Tyagi, S.C. (2005) The central role of vascular extracellular matrix and basement membrane remodeling in metabolic syndrome and type 2 diabetes: the matrix preloaded Cardiovasc Diabetol 4, 9.PubMedCrossRefGoogle Scholar
  25. 25.
    Ryan, U.S., Ryan, J.W., and Whitaker, C. (1979) How do kinins affect vascular tone? Adv Exp Med Biol 120A, 375–391.PubMedGoogle Scholar
  26. 26.
    Nakaoke, R., Verma, S., Niwa, M., Doghu, S., and Banks, W.A. (2007) Glucose regulated blood-brain barrier transport of insulin: Pericyte-astrocyte-endothelial cell cross talk IJNN 3, 195–200.Google Scholar
  27. 27.
    Rucker, H.K., Wynder, H.J., and Thomas, W.E. (2000) Cellular mechanisms of CNS pericytes Brain Res Bull 51, 363–369.PubMedCrossRefGoogle Scholar
  28. 28.
    Carlson, E.C. (1989) Fenestrated subendothelial basement membranes in human retinal capillaries Invest Ophthalmol Vis Sci 30, 1923–1932.PubMedGoogle Scholar
  29. 29.
    Larson, D.M., Haudenschild, C.C., and Beyer, E.C. (1990) Gap junction messenger RNA expression by vascular wall cells Circ Res 66, 1074–1080.PubMedGoogle Scholar
  30. 30.
    Cuevas, P., Gutierrez-Diaz, J. A., Reimers, D., Dujovny, M., Diaz, F. G., and Ausman, J. I. (1984) Pericyte endothelial gap junctions in human cerebral capillaries Anat Embryol (Berl) 170, 155–159.CrossRefGoogle Scholar
  31. 31.
    Nakamura, K., Kamouchi, M., Kitazono, T., Kuroda, J., Matsuo, R., Hagiwara, N., Ishikawa, E., Ooboshi, H., Ibayashi, S., and Iida, M. (2008) Role of NHE1 in calcium signaling and cell proliferation in human CNS pericytes Am J Physiol Heart Circ Physiol 294, H1700–H1707.PubMedCrossRefGoogle Scholar
  32. 32.
    Jójárt, I., Joó, F., Siklós, L., and László, F.A. (1984) Immunoelectronhistochemical evidence for innervation of brain microvessels by vasopressin-immunoreactive neurons in the rat Neurosci Lett 51, 259–264.PubMedCrossRefGoogle Scholar
  33. 33.
    Castejón, O.J. (1980) Electron microscopic study of capillary wall in human cerebral edema J Neuropathol Exp Neurol 39, 296–328.PubMedCrossRefGoogle Scholar
  34. 34.
    Oku, H., Kodama, T., Sakagami, K., and Puro, D.G. (2001) Diabetes-induced disruption of gap junction pathways within the retinal microvasculature Invest Ophthalmol Vis Sci 42, 1915–1920.PubMedGoogle Scholar
  35. 35.
    Kawamura, H., Oku, H., Li, Q., Sakagami, K., and Puro, D.G. (2002) Endothelin-induced changes in the physiology of retinal peri­cytes Invest Ophthalmol Vis Sci 43, 882–888.PubMedGoogle Scholar
  36. 36.
    Li, A.F., Sato, T., Haimovici, R., Okamoto, T., and Roy, S. (2003) High glucose alters connexin 43 expression and gap junction intercellular communication activity in retinal pericytes. Invest Ophthalmol Vis Sci 44, 5376–5382.PubMedCrossRefGoogle Scholar
  37. 37.
    Allt, G., and Lawrenson, J.G. (2001) Pericytes: cell biology and pathology Cells Tissues Organs 169, 1–11PubMedCrossRefGoogle Scholar
  38. 38.
    Virgintino, D., Girolamo, F., Errede, M., Capobianco, C., Robertson, D., Stallcup, W. B., Perris, R., and Roncali, L. (2007) An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis. Angiogenesis 10, 35–45.PubMedCrossRefGoogle Scholar
  39. 39.
    Rauch, S., and Reale, E. (1968) The pericytes (Rouget cells) of the stria vascularis vessels [German]. Arch Klin Exp Ohren Nasen Kehlkopfheilkd 192, 82–90.Google Scholar
  40. 40.
    Rodriguez-Baeza, A., Reina-De La Torre, F., Ortega-Sanchez, M., and Sahuquillo-Barris, J. (1998) Perivascular structures in corrosion casts of the human central nervous system: a confocal laser and scanning electron microscope study Anat Rec 252, 176–184.PubMedCrossRefGoogle Scholar
  41. 41.
    Mottow-Lippa, L., Tso, M.O., Peyman, G.A., and Chejfec, G. (1983) Von Hippel angiomatosis. A light, electron microscopic, and immunoperoxidase characterization Ophthalmology 90, 848–855.PubMedGoogle Scholar
  42. 42.
    Verbeek, M.M., Otte-Höller, I., Wesseling, P., Ruiter, D.J., and de Waal, R.M. (1994) Induction of alpha-smooth muscle actin expression in cultured human brain pericytes by transforming growth factor-beta 1 Am J Pathol 144, 372–382.PubMedGoogle Scholar
  43. 43.
    Liebner, S., Fischmann, A., Rascher, G., Duffner, F., Grote, E. H., Kalbacher, H., and Wolburg, H. (2000) Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol 100, 323–331.PubMedCrossRefGoogle Scholar
  44. 44.
    Kutcher, M.E., Kolyada, A.Y., Surks, H.K., and Herman, I.M. (2007) Pericyte Rho GTPase mediates both pericyte contractile phenotype and capillary endothelial growth state Am J Pathol 171, 693–701.PubMedCrossRefGoogle Scholar
  45. 45.
    Steinach, E., and Kahn, B.H. (1903) Echte Contractilität und motorische Innervation der Blutcapillaren [German] Pflügers Archiv 97, 195.CrossRefGoogle Scholar
  46. 46.
    Anderson, D.R. (1996) Glaucoma, capillaries and pericytes. 1. Blood flow regulation Ophthalmologica 210, 257–262.PubMedCrossRefGoogle Scholar
  47. 47.
    Peppiatt, C.M., Howarth, C., Mobbs, P., and Attwell, D. (2006) Bidirectional control of CNS capillary diameter by pericytes Nature 443, 700–704.PubMedCrossRefGoogle Scholar
  48. 48.
    Dore-Duffy, P., and LaManna, J. C. (2007) Physiologic angiodynamics in the brain Antioxid Redox Signal 9, 1363–1371.PubMedCrossRefGoogle Scholar
  49. 49.
    Quignard, J.F., Harley, E.A., Duhault, J., Vanhoutte, P.M., and Félétou, M. (2003) K+ channels in cultured bovine retinal pericytes: effects of beta-adrenergic stimulation. J Cardiovasc Pharmacol 42, 379–388.PubMedCrossRefGoogle Scholar
  50. 50.
    Cao, C., Goo, J.H., Lee-Kwon, W., and Pallone, T.L. (2006) Vasa recta pericytes express a strong inward rectifier K+ conductance Am J Physiol Regul Integr Comp Physiol 290, R1601–R1607.PubMedGoogle Scholar
  51. 51.
    Jackson, W.F. (2005) Potassium channels in the peripheral microcirculation Microcirculation 12, 113–127.PubMedCrossRefGoogle Scholar
  52. 52.
    Bondjers, C., He, L., Takemoto, M., Norlin, J., Asker, N., Hellström, M., Lindahl, P., and Betsholtz, C. (2006) Microarray analysis of blood microvessels from PDGF-B and PDGF-Rbeta mutant mice identifies novel markers for brain pericytes FASEB J 20, 1703–1705.PubMedCrossRefGoogle Scholar
  53. 53.
    Stallcup, W.B. (2002) The NG2 proteoglycan: past insights and future prospects. J Neurocytol 31, 423–435.PubMedCrossRefGoogle Scholar
  54. 54.
    Balabanov, R., Washington, R., Wagnerova, J., and Dore-Duffy, P. (1996) CNS microvascular pericytes express macrophage-like function, cell surface integrin alpha M, and macrophage marker ED-2. Microvasc Res 52, 127–142.PubMedCrossRefGoogle Scholar
  55. 55.
    Bergers, G., and Song, S. (2005) The role of pericytes in blood-vessel formation and maintenance Neuro Oncol 7, 452–464.PubMedCrossRefGoogle Scholar
  56. 56.
    Bandopadhyay, R., Orte, C., Lawrenson, J.G., Reid, A.R., De Silva, S., and Allt, G. (2001) Contractile proteins in pericytes at the blood-brain and blood-retinal barriers J Neurocytol 30, 35–44.PubMedCrossRefGoogle Scholar
  57. 57.
    Cho, H., Kozasa, T., Bondjers, C., Betsholtz, C., and Kehrl, J.H. (2003) Pericyte-specific expression of Rgs5: implications for PDGF and EDG receptor signaling during vascular maturation FASEB J 17, 440–442.PubMedGoogle Scholar
  58. 58.
    Hellström, M., Kalén, M., Lindahl, P., Abramsson, A., and Betsholtz, C. (1999) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse Development 126, 3047–3055.PubMedGoogle Scholar
  59. 59.
    Schlingemann, R.O., Rietveld, F.J., de Waal, R.M., Ferrone, S., and Ruiter, D.J. (1990) Expression of the high molecular weight melanoma-associated antigen by pericytes during angiogenesis in tumors and in healing wounds. Am J Pathol 136, 1393–1405.PubMedGoogle Scholar
  60. 60.
    Kunz, J., Krause, D., Kremer, M., and Dermietzel, R. (1994) The 140-kDa protein of blood-brain barrier-associated pericytes is identical to aminopeptidase N. J Neurochem 62, 2375–2386.PubMedCrossRefGoogle Scholar
  61. 61.
    Sundberg, C., Kowanetz, M., Brown, L.F., Detmar, M., and Dvorak, H.F. (2002) Stable expression of angiopoietin-1 and other markers by cultured pericytes: phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo. Lab Invest 82, 387–401.PubMedGoogle Scholar
  62. 62.
    Nayak, R.C., Berman, A.B., George, K.L., Eisenbarth, G.S., and King, G.L. (1988) A monoclonal antibody (3G5)-defined ganglioside antigen is expressed on the cell surface of microvascular pericytes J Exp Med 167, 1003–1015.PubMedCrossRefGoogle Scholar
  63. 63.
    Gushi, A., Tanaka, M., Tsuyama, S., Nagai, T., Kanzaki, T., Kanekura, T., and Matsuyama, T. (2008) The 3G5 antigen is expressed in dermal mast cells but not pericytes. J Cutan Pathol 35, 278–284.PubMedCrossRefGoogle Scholar
  64. 64.
    Charbord, P., Oostendorp, R., Pang, W., Herault, O., Noel, F., Tsuji, T., Dzierzak, E., and Peault, B. (2002) Comparative study of stromal cell lines derived from embryonic, fetal, and postnatal mouse blood-forming tissues Exp Hematol 30, 1202–1210.PubMedCrossRefGoogle Scholar
  65. 65.
    Fisher, M. (2009) Pericyte signaling in the neurovascular unit Stroke 40, S13–S15.PubMedCrossRefGoogle Scholar
  66. 66.
    Ni, T.G. (1922) The active response of capillaries of frogs, tadpoles, fish, bats, and men to various forms of excitation. Am J Phys 62, 282–309.Google Scholar
  67. 67.
    Kelley, C., D’Amore, P., Hechtman, H.B., and Shepro, D. (1988) Vasoactive hormones and cAMP affect pericyte contraction and stress fibres in vitro J Muscle Res Cell Motil 9, 184–194.PubMedCrossRefGoogle Scholar
  68. 68.
    Das, A., Frank, R.N., Weber, M.L., Kennedy, A., Reidy, C.A., and Mancini, M.A. (1988) ATP causes retinal pericytes to contract in vitro Exp Eye Res 46, 349–362.PubMedCrossRefGoogle Scholar
  69. 69.
    Edelman, D.A., Jiang, Y., Tyburski, J., Wilson, R.F., and Steffes, C. (2006) Pericytes and their role in microvasculature homeostasis. J Surg Res 135, 305–311.PubMedCrossRefGoogle Scholar
  70. 70.
    Hughes, S., Gardiner, T., Hu, P., Baxter, L., Rosinova, E., and Chan-Ling, T. (2006) Altered pericyte-endothelial relations in the rat retina during aging: implications for vessel stability Neurobiol Aging 27, 1838–1847.PubMedCrossRefGoogle Scholar
  71. 71.
    Yamanishi, S., Katsumura, K., Kobayashi, T., and Puro, D.G. (2006) Extracellular lactate as a dynamic vasoactive signal in the rat retinal microvasculature Am J Physiol Heart Circ Physiol 290, H925–H934.PubMedCrossRefGoogle Scholar
  72. 72.
    King, J.S., and Schwyn, R.C. (1970) The fine structure of neuroglial cells and pericytes in the primate red nucleus and substantia nigra Z Zellforsch Mikrosk Anat 106, 309–321.PubMedCrossRefGoogle Scholar
  73. 73.
    Katenkamp, D., and Stiller, D. (1975) Cellular composition of the so-called dermatofibroma (histiocytoma cutis) Virchows Arch A Pathol Anat Histol 367, 325–336.PubMedCrossRefGoogle Scholar
  74. 74.
    Katenkamp, D., Stiller, D., and Schulze, E. (1976) Ultrastructural cytology of regenerating tendon–an experimental study Exp Pathol (Jena) 12, 25–37.Google Scholar
  75. 75.
    Desmoulière, A., Rubbia-Brandt, L., Abdiu, A., Walz, T., Macieira-Coelho, A., and Gabbiani, G. (1992) Alpha-smooth muscle actin is expressed in a subpopulation of cultured and cloned fibroblasts and is modulated by gamma-interferon Exp Cell Res 201, 64–73.PubMedCrossRefGoogle Scholar
  76. 76.
    Niki, T., Pekny, M., Hellemans, K., Bleser, P. D., Berg, K. V., Vaeyens, F., Quartier, E., Schuit, F., and Geerts, A. (1999) Class VI intermediate filament protein nestin is induced during activation of rat hepatic stellate cells Hepatology 29, 520–527.PubMedCrossRefGoogle Scholar
  77. 77.
    Williams, G.M., and Iatropoulos, M.J. (2002) Alteration of liver cell function and proliferation: differentiation between adaptation and toxicity Toxicol Pathol 30, 41–53.PubMedCrossRefGoogle Scholar
  78. 78.
    Schor, A.M., Canfield, A.E., Sutton, A.B., Allen, T.D., Sloan, P., and Schor, S.L. (1992) The behaviour of pericytes in vitro: relevance to angiogenesis and differentiation EXS 61, 167–178.PubMedGoogle Scholar
  79. 79.
    Diaz-Flores, L., Gutierrez, R., Lopez-Alonso, A., Gonzalez, R., and Varela, H. (1992) Pericytes as a supplementary source of osteoblasts in periosteal osteogenesis Clin Orthop Relat Res 275, 280–286.PubMedGoogle Scholar
  80. 80.
    Brighton, C.T., Lorich, D.G., Kupcha, R., Reilly, T.M., Jones, A.R., and Woodbury, R.A. II. (1992) The pericyte as a possible osteoblast progenitor cell. Clin Orthop Relat Res 275, 287–299.Google Scholar
  81. 81.
    Canfield, A.E., Sutton, A.B., Hoyland, J.A., and Schor, A.M. (1996) Association of thrombospondin-1 with osteogenic differentiation of retinal pericytes in vitro. J Cell Sci 109, 343–353.PubMedGoogle Scholar
  82. 82.
    Reilly, T.M., Seldes, R., Luchetti, W., and Brighton, C.T. (1998) Similarities in the phenotypic expression of pericytes and bone cells Transpl Immunol 346, 95–103.Google Scholar
  83. 83.
    Doherty, M.J., and Canfield, A.E. (1999) Gene expression during vascular pericyte differentiation Crit Rev Eukaryot Gene Expr 9, 1–17.PubMedGoogle Scholar
  84. 84.
    Farrington-Rock, C., Crofts, N.J., Doherty, M.J., Ashton, B.A., Griffin-Jones, C., and Canfield, A.E. (2004) Chondrogenic and adipogenic potential of microvascular pericytes Circulation 110, 2226–2232.PubMedCrossRefGoogle Scholar
  85. 85.
    Galmiche, M. C., Koteliansky, V. E., Briere, J., Herve, P., and Charbord, P. (1993) Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway Blood 82, 66–76.PubMedGoogle Scholar
  86. 86.
    Wenisch, S., Trinkaus, K., Hild, A., Hose, D., Herde, K., Heiss, C., Kilian, O., Alt, V., and Schnettler, R. (2005) Human reaming debris: a source of multipotent stem cells Bone 36, 74–83.PubMedCrossRefGoogle Scholar
  87. 87.
    Nico, B., Mangieri, D., Corsi, P., De Giorgis, M., Vacca, A., Roncali, L., and Ribatti, D. (2004) Vascular endothelial growth factor-A, vascular endothelial growth factor receptor-2 and angiopoietin-2 expression in the mouse choroid plexuses. Brain Res 1013, 256–259.PubMedCrossRefGoogle Scholar
  88. 88.
    Palmer, T.D., Willhoite, A.R., and Gage, F.H. (2000) Vascular niche for adult hippocampal neurogenesis J Comp Neurol 425, 479–494.PubMedCrossRefGoogle Scholar
  89. 89.
    Jin, K., Mao, X. O., Sun, Y., Xie, L., Jin, L., Nishi, E., Klagsbrun, M., and Greenberg, D. A. (2002) Heparin-binding epidermal growth factor-like growth factor: hypoxia-inducible expression in vitro and stimulation of neurogenesis in vitro and in vivo J Neurosci 22, 5365–5373.PubMedGoogle Scholar
  90. 90.
    Louissaint, A. Jr, Rao, S., Leventhal, C., and Goldman, S.A. (2002) Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain Neuron 34, 945–960.PubMedCrossRefGoogle Scholar
  91. 91.
    Chaudhry, A.P., Montes, M., and Cohn, G.A. (1978) Ultrastructure of cerebellar hemangioblastoma Cancer 42, 1834–1850.PubMedCrossRefGoogle Scholar
  92. 92.
    Cinti, S., Cigolini, M., Bosello, O., and Björntorp, P. (1984) A morphological study of the adipocyte precursor J Submicrosc Cytol 16, 243–251.PubMedGoogle Scholar
  93. 93.
    Balabanov, R., Beaumont, T., and Dore-Duffy, P. (1999) Role of central nervous system microvascular pericytes in activation of antigen-primed splenic T-lymphocytes J Neurosci Res 55, 578–587.PubMedCrossRefGoogle Scholar
  94. 94.
    Shen, P. J., Yuan, C. G., Ma, J., Cheng, S., Yao, M., Turnley, A. M., and Gundlach, A. L. (2005) Galanin in neuro(glio)genesis: expression of galanin and receptors by progenitor cells in vivo and in vitro and effects of galanin on neurosphere proliferation. Neuropeptides 39, 201–205.PubMedCrossRefGoogle Scholar
  95. 95.
    Suematsu, M, and Aiso, S. (2001) Professor Toshio Ito: a clairvoyant in pericyte biology Keio J Med 50, 66–71.PubMedGoogle Scholar
  96. 96.
    Lardon, J., Rooman, I., and Bouwens, L. (2002) Nestin expression in pancreatic stellate cells and angiogenic endothelial cells Histochem Cell Biol 117, 535–540.PubMedCrossRefGoogle Scholar
  97. 97.
    Kadoya, K., Fukushi, J., Matsumoto, Y., Yamaguchi, Y., and Stallcup, W. B. (2008) NG2 proteoglycan expression in mouse skin: altered postnatal skin development in the NG2 null mouse J Histochem Cytochem 56, 295–303.PubMedCrossRefGoogle Scholar
  98. 98.
    Rajkumar, V.S., Howell, K., Csiszar, K., Denton, C.P., Black, C.M., and Abraham, D.J. (2005) Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis Arthritis Res Ther 7, R1113–R1123.PubMedCrossRefGoogle Scholar
  99. 99.
    Crisan, M., Zheng, B., Zambidis, E.T., Yap, S., Tavian, M., Sun, B., Giacobino, J-P., Casteilla, L., Huard, J., and Péault, B. (2007) Blood Vessels as a Source of Progenitor Cells in Human Embryonic and Adult Life In: Stem Cells and Their Potential for Clinical Application, in NATO Science for Peace and Security (Bilko, N. M., Fehse, B., Ostertag, W., Stocking, C., Zander, A.R., Ed.), pp 137–147, Springer, Netherlands.Google Scholar
  100. 100.
    Dellavalle, A., Sampaolesi, M., Tonlorenzi, R., Tagliafico, E., Sacchetti, B., Perani, L., Innocenzi, A., Galvez, B. G., Messina, G., Morosetti, R., Li, S., Belicchi, M., Peretti, G., Chamberlain, J. S., Wright, W. E., Torrente, Y., Ferrari, S., Bianco, P., and Cossu, G. (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells Nat Cell Biol 9, 255–267.PubMedCrossRefGoogle Scholar
  101. 101.
    Péault, B., Rudnicki, M., Torrente, Y., Cossu, G., Tremblay, J. P., Partridge, T., Gussoni, E., Kunkel, L. M., and Huard, J. (2007) Stem and progenitor cells in skeletal muscle development, maintenance, and therapy Mol Ther 15, 867–877.PubMedCrossRefGoogle Scholar
  102. 102.
    Davidoff, M.S., Middendorff, R., Enikolopov, G., Riethmacher, D., Holstein, A.F., and Müller, D. (2004) Progenitor cells of the testosterone-producing Leydig cells revealed J Cell Biol 167, 935–944.PubMedCrossRefGoogle Scholar
  103. 103.
    Lovschall, H., Mitsiadis, T.A., Poulsen, K., Jensen, K.H., and Kjeldsen, A.L. (2007) Coexpression of Notch3 and Rgs5 in the pericyte-vascular smooth muscle cell axis in response to pulp injury Int J Dev Biol 51, 715–721.PubMedCrossRefGoogle Scholar
  104. 104.
    Puri, P. L., Bhakta, K., Wood, L. D., Costanzo, A., Zhu, J., and Wang, J. Y. (2002) A myogenic differentiation checkpoint activated by genotoxic stress Nat Genet 32, 585–593.PubMedCrossRefGoogle Scholar
  105. 105.
    Song, S., Ewald, A. J., Stallcup, W., Werb, Z., and Bergers, G. (2005) PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival Nat Cell Biol 7, 870–879.PubMedCrossRefGoogle Scholar
  106. 106.
    Gerhardt, H., and Betsholtz, C. (2003) Endothelial-pericyte interactions in angiogenesis Cell Tissue Res 314, 15–23.PubMedCrossRefGoogle Scholar
  107. 107.
    Mancuso MR, Kuhnert F, Kuo C.J. (2008) Developmental angiogenesis of the central nervous system Lymphat Res Biol 6, 173–180.PubMedCrossRefGoogle Scholar
  108. 108.
    Wang, L., Chopp, M., Gregg, S.R., Zhang, R.L., Teng, H., Jiang, A., Feng, Y., and Zhang, Z.G. (2008) Neural progenitor cells treated with EPO induce angiogenesis through the production of VEGF J Cereb Blood Flow Metab 28, 1361–1318.PubMedCrossRefGoogle Scholar
  109. 109.
    Yonekura, H., Sakurai, S., Liu, X., Migita, H., Wang, H., Yamagishi, S., Nomura, M., Abedin, M. J., Unoki, H., Yamamoto, Y., and Yamamoto, H. (1999) Placenta growth factor and vascular endothelial growth factor B and C expression in microvascular endothelial cells and pericytes. Implication in autocrine and paracrine regulation of angiogenesis J Biol Chem 274, 35172–35178.PubMedCrossRefGoogle Scholar
  110. 110.
    de la Fuente, R., Abad, J. L., Garcia-Castro, J., Fernandez-Miguel, G., Petriz, J., Rubio, D., Vicario-Abejon, C., Guillen, P., Gonzalez, M. A., and Bernad, A. (2004) Dedifferentiated adult articular chondrocytes: a population of human multipotent primitive cells Exp Cell Res 297, 313–328.PubMedCrossRefGoogle Scholar
  111. 111.
    Greenberg, J.I., Shields, D.J., Barillas, S.G., Acevedo, L.M., Murphy, E., Huang, J., Scheppke, L., Stockmann, C., Johnson, R.S., Angle, N., and Cheresh, D.A. (2008) A role for VEGF as a negative regulator of pericyte function and vessel maturation Nature 456, 809–813.PubMedCrossRefGoogle Scholar
  112. 112.
    Dore-Duffy, P., Wang, X., Mehedi, A., Kreipke, C.W., and Rafols, J.A. (2007) Differential expression of capillary VEGF isoforms following traumatic brain injury Neurol Res 29: 395–403.PubMedCrossRefGoogle Scholar
  113. 113.
    Diaz-Flores, L., Gutierrez, R., Valladares, F., Varela, H., and Perez, M. (1994) Intense vascular sprouting from rat femoral vein induced by prostaglandins E1 and E2 Anat Rec 238, 68–76.PubMedCrossRefGoogle Scholar
  114. 114.
    Nehls, V., Denzer, K., and Drenckhahn, D. (1992) Pericyte involvement in capillary sprouting during angiogenesis in situ Cell Tissue Res 270, 469-474.PubMedCrossRefGoogle Scholar
  115. 115.
    Pfister, F., Feng, Y., vom Hagen, F., Hoffmann, S., Molema, G., Hillebrands, J. L., Shani, M., Deutsch, U., and Hammes, H. P. (2008) Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy Diabetes 57, 2495–2502.Google Scholar
  116. 116.
    Duz, B., Oztas, E., Erginay, T., Erdogan, E., and Gonul, E. (2007) The effect of moderate hypothermia in acute ischemic stroke on pericyte migration: an ultrastructural study Cryobiology 55, 279–284.PubMedCrossRefGoogle Scholar
  117. 117.
    Claudio, L., and Brosnan, C. F. (1992) Effects of prazosin on the blood-brain barrier during experimental autoimmune encephalomyelitis Brain Res 594, 233–243.PubMedCrossRefGoogle Scholar
  118. 118.
    Kunz, J., Krause, D., Gehrmann, J., and Dermietzel, R. (1995) Changes in the expression pattern of blood-brain barrier-associated pericytic aminopeptidase N (pAP N) in the course of acute experimental autoimmune encephalomyelitis J Neuroimmunol 59, 41–55.PubMedCrossRefGoogle Scholar
  119. 119.
    Dore-Duffy, P., Balabanov, R., Rafols, J., and Swanborg, R. H. (1996) Recovery phase of acute experimental autoimmune encephalomyelitis in rats corresponds to development of endothelial cell unresponsiveness to interferon gamma activation J Neurosci Res 44, 223–234.PubMedCrossRefGoogle Scholar
  120. 120.
    Bolton, C. (1997) Neurovascular damage in experimental allergic encephalomyelitis: a target for pharmacological control Mediators Inflamm 6, 295–302.PubMedCrossRefGoogle Scholar
  121. 121.
    Zlokovic, B. V. (2008) The blood-brain barrier in health and chronic neurodegenerative disorders Neuron 57, 178–201.PubMedCrossRefGoogle Scholar
  122. 122.
    Ho, K. L. (1985) Ultrastructure of cerebellar capillary hemangioblastoma. IV. Pericytes and their relationship to endothelial cells Acta Neuropathol 67, 254–264.PubMedCrossRefGoogle Scholar
  123. 123.
    Winkler, F., Kozin, S. V., Tong, R. T., Chae, S. S., Booth, M. F., Garkavtsev, I., Xu, L., Hicklin, D. J., Fukumura, D., di Tomaso, E., Munn, L. L., and Jain, R. K. (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases Cancer Cell 6, 553–563.PubMedGoogle Scholar
  124. 124.
    Hammes, H. P., Lin, J., Renner, O., Shani, M., Lundqvist, A., Betsholtz, C., Brownlee, M., and Deutsch, U. (2002) Pericytes and the pathogenesis of diabetic retinopathy Diabetes 51, 3107–3112.PubMedCrossRefGoogle Scholar
  125. 125.
    Frank, R. N., Turczyn, T. J., and Das, A. (1990) Pericyte coverage of retinal and cerebral capillaries Invest Ophthalmol Vis Sci 31, 999–1007.PubMedGoogle Scholar
  126. 126.
    Feng, Y., Pfister, F., Schreiter, K., Wang, Y., Stock, O., Vom Hagen, F., Wolburg, H., Hoffmann, S., Deutsch, U., and Hammes, H. P. (2008) Angiopoietin-2 deficiency decelerates age-dependent vascular changes in the mouse retina Cell Physiol Biochem 21, 129–136.PubMedCrossRefGoogle Scholar
  127. 127.
    Szpak, G. M., Lewandowska, E., Wierzba-Bobrowicz, T., Bertrand, E., Pasennik, E., Mendel, T., Stepien, T., Leszczynska, A., and Rafalowska, J. (2007) Small cerebral vessel disease in familial amyloid and non-amyloid angiopathies: FAD-PS-1 (P117L) mutation and CADASIL. Immunohistochemical and ultrastructural studies Folia Neuropathol 45, 192–204.PubMedGoogle Scholar
  128. 128.
    Wegiel, J., and Wisniewski, H. M. (1992) Tubuloreticular structures in microglial cells, pericytes and endothelial cells in Alzheimer’s disease Acta Neuropathol 83, 653–658.PubMedCrossRefGoogle Scholar
  129. 129.
    Stewart, P. A., Hayakawa, K., Akers, M. A., and Vinters, H. V. (1992) A morphometric study of the blood-brain barrier in Alzheimer’s disease Lab Invest 67, 734–742.PubMedGoogle Scholar
  130. 130.
    Yamagishi, S., and Imaizumi, T. (2005) Pericyte biology and diseases Int J Tissue React 27, 125–135.PubMedGoogle Scholar
  131. 131.
    Kischer, C. W. (1992) The microvessels in hypertrophic scars, keloids and related lesions: a review J Submicrosc Cytol Pathol 24, 281–296.PubMedGoogle Scholar
  132. 132.
    Li, W., Yanoff, M., Liu, X., and Ye, X. (1997) Retinal capillary pericyte apoptosis in early human diabetic retinopathy Chin Med J (Engl) 110, 659–663.Google Scholar
  133. 133.
    Shojaee, N., Patton, W. F., Hechtman, H. B., and Shepro, D. (1999) Myosin translocation in retinal pericytes during free-radical induced apoptosis J Cell Biochem 75, 118–129.PubMedCrossRefGoogle Scholar
  134. 134.
    Zagzag, D., Amirnovin, R., Greco, M. A., Yee, H., Holash, J., Wiegand, S. J., Zabski, S., Yancopoulos, G. D., and Grumet, M. (2000) Vascular apoptosis and involution in gliomas precede neovascularization: a novel concept for glioma growth and angiogenesis Lab Invest 80, 837–849.PubMedGoogle Scholar
  135. 135.
    Machein, M. R., Knedla, A., Knoth, R., Wagner, S., Neuschl, E., and Plate, K. H. (2004) Angiopoietin-1 promotes tumor angiogenesis in a rat glioma model. Am J Pathol 165, 1557–1570.PubMedGoogle Scholar
  136. 136.
    Vermeulen, P. B., Colpaert, C., Salgado, R., Royers, R., Hellemans, H., Van Den Heuvel, E., Goovaerts, G., Dirix, L. Y., and Van Marck, E. (2001) Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasiaJ Pathol 195, 336–342.PubMedCrossRefGoogle Scholar
  137. 137.
    Bexell, D., Gunnarsson, S., Tormin, A., Darabi, A., Gisselsson, D., Roybon, L., Scheding, S., and Bengzon, J. (2009) Bone marrow multipotent mesenchymal stroma cells act as pericyte-like migratory vehicles in experimental gliomas Mol Ther 17, 183–190.PubMedCrossRefGoogle Scholar
  138. 138.
    Li, W., Liu, X., Yanoff, M., Cohen, S., and Ye, X. (1996) Cultured retinal capillary pericytes die by apoptosis after an abrupt fluctuation from high to low glucose levels: a comparative study with retinal capillary endothelial cells Diabetologia 39, 537–547.PubMedCrossRefGoogle Scholar
  139. 139.
    Zhu, M., Madigan, M. C., van Driel, D., Maslim, J., Billson, F. A., Provis, J. M., and Penfold, P. L. (2000) The human hyaloid system: cell death and vascular regression Exp Eye Res 70, 767–776.PubMedCrossRefGoogle Scholar
  140. 140.
    Braun, A., Xu, H., Hu, F., Kocherlakota, P., Siegel, D., Chander, P., Ungvari, Z., Csiszar, A., Nedergaard, M., and Ballabh, P. (2007) Paucity of pericytes in germinal matrix vasculature of premature infants J Neurosci 27, 12012–12024.PubMedCrossRefGoogle Scholar
  141. 141.
    Khoury, J., and Langleben, D. (1996) Platelet-activating factor stimulates lung pericyte growth in vitro Am J Physiol 270, L298–L304.PubMedGoogle Scholar
  142. 142.
    Seifert, M., and Reichrath, J. (2006) The role of the human DNA mismatch repair gene hMSH2 in DNA repair, cell cycle control and apoptosis: implications for pathogenesis, progression and therapy of cancer J Mol Histol 37, 301–307.PubMedCrossRefGoogle Scholar
  143. 143.
    Heyer, J., Yang, K., Lipkin, M., Edelmann, W., and Kucherlapati, R. (1999) Mouse models for colorectal cancer Oncogene 18, 5325–5333.PubMedCrossRefGoogle Scholar
  144. 144.
    Canfield, A.E., Farrington, C., Dziobon, M.D., Boot-Handford, R.P., Heagerty, A.M., Kumar, S.N., and Roberts, I.S. (2002) The involvement of matrix glycoproteins in vascular calcification and fibrosis: an immunohistochemical study J Pathol 196, 228–234.PubMedCrossRefGoogle Scholar
  145. 145.
    Nehls V, and Drenckhahn D. (1991) Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin J Cell Biol 113, 147–154.PubMedCrossRefGoogle Scholar
  146. 146.
    Newcomb, P.M., and Herman, IM. (1993) Pericyte growth and contractile phenotype: modulation by endothelial-synthesized matrix and comparison with aortic smooth muscle J Cell Physiol 155, 385–393.PubMedCrossRefGoogle Scholar
  147. 147.
    Verbeek, M.M., Westphal, J.R., Ruiter, D.J., and de Waal, R.M. (1995) T lymphocyte adhesion to human brain pericytes is mediated via very late antigen-4/vascular cell adhesion molecule-1 interactions. J Immunol 154, 5876–5884.PubMedGoogle Scholar
  148. 148.
    Fujimoto, T., and Singer, S.J. (1987) Immunocytochemical studies of desmin and vimentin in pericapillary cells of chicken J Histochem Cytochem 35, 1105–1115.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of NeurologyWayne State University School of MedicineDetroitUSA

Personalised recommendations