Pericytes: The Role of Multipotent Stem Cells in Vascular Maintenance and Regenerative Medicine

  • Toka A. Ahmed
  • Nagwa El-BadriEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1079)


Blood vessels consist of an inner endothelial cell layer lining the vessel wall and perivascular pericytes, also known as mural cells, which envelop the vascular tube surface. Pericytes have recently been recognized for their central role in blood vessel formation. Pericytes are multipotent cells that are heterogeneous in their origin, function, morphology and surface markers. Similar to other types of stem cells, pericytes act as a repair system in response to injury by maintaining the structural integrity of blood vessels. Several studies have shown that blood vessels lacking pericytes become hyperdilated and haemorrhagic, leading to vascular complications ranging from diabetic retinopathy to embryonic death. The role of pericytes is not restricted to the formation and development of the vasculature: they have been shown to possess stem cell-like characteristics and may differentiate into cell types from different lineages. Recent discoveries regarding the contribution of pericytes to tumour metastasis and the maintenance of tumour vascular supply and angiogenesis have led researchers to propose targeting pericytes with anti-angiogenic therapies. In this review, we will examine the different physiological roles of pericytes, their differentiation potential, and how they interact with surrounding cells to ensure the integrity of blood vessel formation and maintenance.


Blood vessel integrity Endothelial cells MSCs Pericytes Vascular mural cells 


  1. Abbott NJ (2002) Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200(6):629–638PubMedPubMedCentralCrossRefGoogle Scholar
  2. Al Ahmad A, Taboada CB, Gassmann M, Ogunshola OO (2011) Astrocytes and pericytes differentially modulate blood-brain barrier characteristics during development and hypoxic insult. J Cereb Blood Flow Metab 31(2):693–705PubMedPubMedCentralCrossRefGoogle Scholar
  3. Allt G, Lawrenson JG (2001) Pericytes: cell biology and pathology. Cells Tissues Organs 169(1):1–11PubMedPubMedCentralCrossRefGoogle Scholar
  4. Antonelli-Orlidge A, Saunders KB, Smith SR, D’Amore PA (1989) An activated form of transforming growth factor beta is produced by cocultures of endothelial cells and pericytes. Proc Natl Acad Sci U S A 86(12):4544–4548PubMedPubMedCentralCrossRefGoogle Scholar
  5. Armulik A, Abramsson A, Betsholtz C (2005) Endothelial/pericyte interactions. Circ Res 97(6):512–523PubMedPubMedCentralCrossRefGoogle Scholar
  6. Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C, He L, Norlin J, Lindblom P, Strittmatter K et al (2010) Pericytes regulate the blood-brain barrier. Nature 468(7323):557–561PubMedCrossRefGoogle Scholar
  7. Armulik A, Genove G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21(2):193–215PubMedPubMedCentralCrossRefGoogle Scholar
  8. Arroyo AG, Iruela-Arispe ML (2010) Extracellular matrix, inflammation, and the angiogenic response. Cardiovasc Res 86(2):226–235PubMedPubMedCentralCrossRefGoogle Scholar
  9. Asahina K, Zhou B, Pu WT, Tsukamoto H (2011) Septum transversum-derived mesothelium gives rise to hepatic stellate cells and perivascular mesenchymal cells in developing mouse liver. Hepatology 53(3):983–995PubMedPubMedCentralCrossRefGoogle Scholar
  10. Babitt JL, Lin HY (2012) Mechanisms of anemia in CKD. J Am Soc Nephrol 23(10):1631–1634PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bachmann S, Le Hir M, Eckardt KU (1993) Co-localization of erythropoietin mRNA and ecto-5′-nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin. J Histochem Cytochem 41(3):335–341CrossRefPubMedGoogle Scholar
  12. Balabanov R, Dore-Duffy P (1998) Role of the CNS microvascular pericyte in the blood-brain barrier. J Neurosci Res 53(6):637–644PubMedPubMedCentralCrossRefGoogle Scholar
  13. Balabanov R, Washington R, Wagnerova J, Dore-Duffy P (1996) CNS microvascular pericytes express macrophage-like function, cell surface integrin alpha M, and macrophage marker ED-2. Microvasc Res 52(2):127–142PubMedPubMedCentralCrossRefGoogle Scholar
  14. Balabanov R, Beaumont T, Dore-Duffy P (1999) Role of central nervous system microvascular pericytes in activation of antigen-primed splenic T-lymphocytes. J Neurosci Res 55(5):578–587PubMedPubMedCentralCrossRefGoogle Scholar
  15. Ballabh P, Braun A, Nedergaard M (2004) The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16(1):1–13PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, Zlokovic BV (2010) Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 68(3):409–427PubMedPubMedCentralCrossRefGoogle Scholar
  17. Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3(6):401–410PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bergers G, Song S (2005) The role of pericytes in blood-vessel formation and maintenance. Neuro-Oncology 7(4):452–464.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Bergwerff M, Verberne ME, DeRuiter MC, Poelmann RE, Gittenberger-de Groot AC (1998) Neural crest cell contribution to the developing circulatory system: implications for vascular morphology? Circ Res 82(2):221–231PubMedPubMedCentralCrossRefGoogle Scholar
  20. Betsholtz C (2004) Insight into the physiological functions of PDGF through genetic studies in mice. Cytokine Growth Factor Rev 15(4):215–228PubMedCrossRefGoogle Scholar
  21. Birbrair A, Zhang T, Files DC, Mannava S, Smith T, Wang ZM, Messi ML, Mintz A, Delbono O (2014a) Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner. Stem Cell Res Ther 5(6):122PubMedPubMedCentralCrossRefGoogle Scholar
  22. Birbrair A, Zhang T, Wang ZM, Messi ML, Olson JD, Mintz A, Delbono O (2014b) Type-2 pericytes participate in normal and tumoral angiogenesis. Am J Physiol Cell Physiol 307(1):C25–C38PubMedPubMedCentralCrossRefGoogle Scholar
  23. Bouchard BA, Shatos MA, Tracy PB (1997) Human brain pericytes differentially regulate expression of procoagulant enzyme complexes comprising the extrinsic pathway of blood coagulation. Arterioscler Thromb Vasc Biol 17(1):1–9PubMedCrossRefGoogle Scholar
  24. Cai CL, Martin JC, Sun Y, Cui L, Wang L, Ouyang K, Yang L, Bu L, Liang X, Zhang X et al (2008) A myocardial lineage derives from Tbx18 epicardial cells. Nature 454(7200):104–108PubMedPubMedCentralCrossRefGoogle Scholar
  25. Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213(2):341–347PubMedCrossRefGoogle Scholar
  26. Caplan AI (2008) All MSCs are pericytes? Cell Stem Cell 3(3):229–230CrossRefPubMedGoogle Scholar
  27. Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, De Mol M, Wu Y, Bono F, Devy L, Beck H et al (2001) Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 7(5):575–583CrossRefPubMedGoogle Scholar
  28. Chang H, Huylebroeck D, Verschueren K, Guo Q, Matzuk MM, Zwijsen A (1999) Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development 126(8):1631–1642PubMedGoogle Scholar
  29. Chen S, Kulik M, Lechleider RJ (2003) Smad proteins regulate transcriptional induction of the SM22alpha gene by TGF-beta. Nucleic Acids Res 31(4):1302–1310PubMedPubMedCentralCrossRefGoogle Scholar
  30. Chen CW, Montelatici E, Crisan M, Corselli M, Huard J, Lazzari L, Peault B (2009) Perivascular multi-lineage progenitor cells in human organs: regenerative units, cytokine sources or both? Cytokine Growth Factor Rev 20(5–6):429–434PubMedPubMedCentralCrossRefGoogle Scholar
  31. Chen CW, Okada M, Proto JD, Gao X, Sekiya N, Beckman SA, Corselli M, Crisan M, Saparov A, Tobita K et al (2013) Human pericytes for ischemic heart repair. Stem Cells 31(2):305–316PubMedPubMedCentralCrossRefGoogle Scholar
  32. Chen WC, Baily JE, Corselli M, Diaz ME, Sun B, Xiang G, Gray GA, Huard J, Peault B (2015) Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity. Stem Cells 33(2):557–573PubMedPubMedCentralCrossRefGoogle Scholar
  33. Cleaver O, Melton DA (2003) Endothelial signaling during development. Nat Med 9(6):661–668PubMedPubMedCentralCrossRefGoogle Scholar
  34. Creazzo TL, Godt RE, Leatherbury L, Conway SJ, Kirby ML (1998) Role of cardiac neural crest cells in cardiovascular development. Annu Rev Physiol 60:267–286PubMedPubMedCentralCrossRefGoogle Scholar
  35. Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301–313PubMedPubMedCentralCrossRefGoogle Scholar
  36. Cuevas P, Gutierrez-Diaz JA, Reimers D, Dujovny M, Diaz FG, Ausman JI (1984) Pericyte endothelial gap junctions in human cerebral capillaries. Anat Embryol (Berl) 170(2):155–159CrossRefGoogle Scholar
  37. da Silva Meirelles L, Caplan AI, Nardi NB (2008) In search of the in vivo identity of mesenchymal stem cells. Stem Cells 26(9):2287–2299PubMedPubMedCentralCrossRefGoogle Scholar
  38. Daneman R, Zhou L, Kebede AA, Barres BA (2010) Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468(7323):562–566PubMedPubMedCentralCrossRefGoogle Scholar
  39. Dar A, Domev H, Ben-Yosef O, Tzukerman M, Zeevi-Levin N, Novak A, Germanguz I, Amit M, Itskovitz-Eldor J (2012) Multipotent vasculogenic pericytes from human pluripotent stem cells promote recovery of murine ischemic limb. Circulation 125(1):87–99CrossRefPubMedGoogle Scholar
  40. DeRuiter MC, Poelmann RE, VanMunsteren JC, Mironov V, Markwald RR, Gittenberger-de Groot AC (1997) Embryonic endothelial cells transdifferentiate into mesenchymal cells expressing smooth muscle actins in vivo and in vitro. Circ Res 80(4):444–451CrossRefPubMedGoogle Scholar
  41. Dettman RW, Denetclaw W Jr, Ordahl CP, Bristow J (1998) Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Dev Biol 193(2):169–181CrossRefPubMedGoogle Scholar
  42. Diaz-Flores L, Gutierrez R, Madrid JF, Varela H, Valladares F, Acosta E, Martin-Vasallo P, Diaz-Flores L Jr (2009) Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. Histol Histopathol 24(7):909–969PubMedGoogle Scholar
  43. Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ (1995) Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 121(6):1845–1854PubMedPubMedCentralGoogle Scholar
  44. Dohgu S, Takata F, Yamauchi A, Nakagawa S, Egawa T, Naito M, Tsuruo T, Sawada Y, Niwa M, Kataoka Y (2005) Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-beta production. Brain Res 1038(2):208–215PubMedPubMedCentralCrossRefGoogle Scholar
  45. Dore-Duffy P (2008) Pericytes: pluripotent cells of the blood brain barrier. Curr Pharm Des 14(16):1581–1593PubMedPubMedCentralCrossRefGoogle Scholar
  46. Dore-Duffy P, Katychev A, Wang X, Van Buren E (2006) CNS microvascular pericytes exhibit multipotential stem cell activity. J Cereb Blood Flow Metab 26(5):613–624PubMedPubMedCentralCrossRefGoogle Scholar
  47. Dulauroy S, Di Carlo SE, Langa F, Eberl G, Peduto L (2012) Lineage tracing and genetic ablation of ADAM12(+) perivascular cells identify a major source of profibrotic cells during acute tissue injury. Nat Med 18(8):1262–1270PubMedPubMedCentralCrossRefGoogle Scholar
  48. Eliasberg CD, Dar A, Jensen AR, Murray IR, Hardy WR, Kowalski TJ, Garagozlo CA, Natsuhara KM, Khan AZ, McBride OJ et al (2017) Perivascular stem cells diminish muscle atrophy following massive rotator cuff tears in a small animal model. J Bone Joint Surg Am 99(4):331–341PubMedPubMedCentralCrossRefGoogle Scholar
  49. Ema M, Faloon P, Zhang WJ, Hirashima M, Reid T, Stanford WL, Orkin S, Choi K, Rossant J (2003) Combinatorial effects of Flk1 and Tal1 on vascular and hematopoietic development in the mouse. Genes Dev 17(3):380–393PubMedPubMedCentralCrossRefGoogle Scholar
  50. Etchevers HC, Couly G, Le Douarin NM (2002) Morphogenesis of the branchial vascular sector. Trends Cardiovasc Med 12(7):299–304CrossRefPubMedGoogle Scholar
  51. Fabry Z, Fitzsimmons KM, Herlein JA, Moninger TO, Dobbs MB, Hart MN (1993) Production of the cytokines interleukin 1 and 6 by murine brain microvessel endothelium and smooth muscle pericytes. J Neuroimmunol 47(1):23–34CrossRefPubMedGoogle Scholar
  52. Farrington-Rock C, Crofts NJ, Doherty MJ, Ashton BA, Griffin-Jones C, Canfield AE (2004) Chondrogenic and adipogenic potential of microvascular pericytes. Circulation 110(15):2226–2232.CrossRefPubMedGoogle Scholar
  53. Fisher M (2009) Pericyte signaling in the neurovascular unit. Stroke 40(3 Suppl):S13–S15CrossRefPubMedGoogle Scholar
  54. Foster K, Sheridan J, Veiga-Fernandes H, Roderick K, Pachnis V, Adams R, Blackburn C, Kioussis D, Coles M (2008) Contribution of neural crest-derived cells in the embryonic and adult thymus. J Immunol 180(5):3183–3189CrossRefPubMedGoogle Scholar
  55. Friedman SL, Arthur MJ (1989) Activation of cultured rat hepatic lipocytes by Kupffer cell conditioned medium. Direct enhancement of matrix synthesis and stimulation of cell proliferation via induction of platelet-derived growth factor receptors. J Clin Invest 84(6):1780–1785PubMedPubMedCentralCrossRefGoogle Scholar
  56. Gaengel K, Genove G, Armulik A, Betsholtz C (2009) Endothelial-mural cell signaling in vascular development and angiogenesis. Arterioscler Thromb Vasc Biol 29(5):630–638CrossRefPubMedGoogle Scholar
  57. Gerhardt H, Betsholtz C (2003) Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314(1):15–23CrossRefPubMedGoogle Scholar
  58. Gerhardt H, Wolburg H, Redies C (2000) N-cadherin mediates pericytic-endothelial interaction during brain angiogenesis in the chicken. Dev Dyn 218(3):472–479CrossRefPubMedGoogle Scholar
  59. Goumans MJ, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P, ten Dijke P (2002) Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J 21(7):1743–1753PubMedPubMedCentralCrossRefGoogle Scholar
  60. Hart CE, Forstrom JW, Kelly JD, Seifert RA, Smith RA, Ross R, Murray MJ, Bowen-Pope DF (1988) Two classes of PDGF receptor recognize different isoforms of PDGF. Science 240(4858):1529–1531CrossRefPubMedGoogle Scholar
  61. Hayashi K, Nakao S, Nakaoke R, Nakagawa S, Kitagawa N, Niwa M (2004) Effects of hypoxia on endothelial/pericytic co-culture model of the blood-brain barrier. Regul Pept 123(1–3):77–83CrossRefPubMedGoogle Scholar
  62. He W, Nieponice A, Soletti L, Hong Y, Gharaibeh B, Crisan M, Usas A, Peault B, Huard J, Wagner WR et al (2010) Pericyte-based human tissue engineered vascular grafts. Biomaterials 31(32):8235–8244PubMedPubMedCentralCrossRefGoogle Scholar
  63. Hellstrom M, Kalen M, Lindahl P, Abramsson A, 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(14):3047–3055PubMedGoogle Scholar
  64. Hellstrom M, Gerhardt H, Kalen M, Li X, Eriksson U, Wolburg H, Betsholtz C (2001) Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol 153(3):543–553PubMedPubMedCentralCrossRefGoogle Scholar
  65. Herrmann M, Bara JJ, Sprecher CM, Menzel U, Jalowiec JM, Osinga R, Scherberich A, Alini M, Verrier S (2016) Pericyte plasticity – comparative investigation of the angiogenic and multilineage potential of pericytes from different human tissues. Eur Cell Mater 31:236–249CrossRefPubMedGoogle Scholar
  66. Hirschi KK, D’Amore PA (1996) Pericytes in the micro-vasculature. Cardiovasc Res 32(4):687–698.CrossRefPubMedGoogle Scholar
  67. Hung CF, Mittelsteadt KL, Brauer R, McKinney BL, Hallstrand TS, Parks WC, Chen P, Schnapp LM, Liles WC, Duffield JS et al (2017) Lung pericyte-like cells are functional interstitial immune sentinel cells. Am J Physiol Lung Cell Mol Physiol 312(4):L556–L567PubMedPubMedCentralCrossRefGoogle Scholar
  68. Ishitsuka K, Ago T, Arimura K, Nakamura K, Tokami H, Makihara N, Kuroda J, Kamouchi M, Kitazono T (2012) Neurotrophin production in brain pericytes during hypoxia: a role of pericytes for neuroprotection. Microvasc Res 83(3):352–359CrossRefPubMedGoogle Scholar
  69. Jansson D, Rustenhoven J, Feng S, Hurley D, Oldfield RL, Bergin PS, Mee EW, Faull RL, Dragunow M (2014) A role for human brain pericytes in neuroinflammation. J Neuroinflammation 11:104PubMedPubMedCentralCrossRefGoogle Scholar
  70. Jung KH, Chu K, Lee ST, Bahn JJ, Jeon D, Kim JH, Kim S, Won CH, Kim M, Lee SK et al (2011) Multipotent PDGFRbeta-expressing cells in the circulation of stroke patients. Neurobiol Dis 41(2):489–497PubMedPubMedCentralCrossRefGoogle Scholar
  71. Kamouchi M, Ago T, Kitazono T (2011) Brain pericytes: emerging concepts and functional roles in brain homeostasis. Cell Mol Neurobiol 31(2):175–193PubMedPubMedCentralCrossRefGoogle Scholar
  72. Karow M, Sanchez R, Schichor C, Masserdotti G, Ortega F, Heinrich C, Gascon S, Khan MA, Lie DC, Dellavalle A et al (2012) Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells. Cell Stem Cell 11(4):471–476PubMedPubMedCentralCrossRefGoogle Scholar
  73. Katare R, Riu F, Mitchell K, Gubernator M, Campagnolo P, Cui Y, Fortunato O, Avolio E, Cesselli D, Beltrami AP et al (2011) Transplantation of human pericyte progenitor cells improves the repair of infarcted heart through activation of an angiogenic program involving micro-RNA-132. Circ Res 109(8):894–906PubMedPubMedCentralCrossRefGoogle Scholar
  74. Kida Y, Duffield JS (2011) Pivotal role of pericytes in kidney fibrosis. Clin Exp Pharmacol Physiol 38(7):467–473PubMedPubMedCentralCrossRefGoogle Scholar
  75. Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ (2005) SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121(7):1109–1121PubMedPubMedCentralCrossRefGoogle Scholar
  76. Kim JA, Tran ND, Li Z, Yang F, Zhou W, Fisher MJ (2006) Brain endothelial hemostasis regulation by pericytes. J Cereb Blood Flow Metab 26(2):209–217PubMedPubMedCentralCrossRefGoogle Scholar
  77. Kirton JP, Crofts NJ, George SJ, Brennan K, Canfield AE (2007) Wnt/beta-catenin signaling stimulates chondrogenic and inhibits adipogenic differentiation of pericytes: potential relevance to vascular disease? Circ Res 101(6):581–589PubMedPubMedCentralCrossRefGoogle Scholar
  78. Knittel T, Dinter C, Kobold D, Neubauer K, Mehde M, Eichhorst S, Ramadori G (1999) Expression and regulation of cell adhesion molecules by hepatic stellate cells (HSC) of rat liver: involvement of HSC in recruitment of inflammatory cells during hepatic tissue repair. Am J Pathol 154(1):153–167PubMedPubMedCentralCrossRefGoogle Scholar
  79. Konig MA, Canepa DD, Cadosch D, Casanova E, Heinzelmann M, Rittirsch D, Plecko M, Hemmi S, Simmen HP, Cinelli P et al (2016) Direct transplantation of native pericytes from adipose tissue: a new perspective to stimulate healing in critical size bone defects. Cytotherapy 18(1):41–52PubMedPubMedCentralCrossRefGoogle Scholar
  80. Korn J, Christ B, Kurz H (2002) Neuroectodermal origin of brain pericytes and vascular smooth muscle cells. J Comp Neurol 442(1):78–88PubMedPubMedCentralCrossRefGoogle Scholar
  81. Kristensson K, Olsson Y (1973) Accumulation of protein tracers in pericytes of the central nervous system following systemic injection in immature mice. Acta Neurol Scand 49(2):189–194PubMedPubMedCentralCrossRefGoogle Scholar
  82. Krueger M, Bechmann I (2010) CNS pericytes: concepts, misconceptions, and a way out. Glia 58(1):1–10PubMedPubMedCentralCrossRefGoogle Scholar
  83. Kutcher ME, Herman IM (2009) The pericyte: cellular regulator of microvascular blood flow. Microvasc Res 77(3):235–246PubMedPubMedCentralCrossRefGoogle Scholar
  84. Lan Y, Liu B, Yao H, Li F, Weng T, Yang G, Li W, Cheng X, Mao N, Yang X (2007) Essential role of endothelial Smad4 in vascular remodeling and integrity. Mol Cell Biol 27(21):7683–7692PubMedPubMedCentralCrossRefGoogle Scholar
  85. Larson DM, Carson MP, Haudenschild CC (1987) Junctional transfer of small molecules in cultured bovine brain microvascular endothelial cells and pericytes. Microvasc Res 34(2):184–199PubMedPubMedCentralCrossRefGoogle Scholar
  86. Larsson J, Goumans MJ, Sjostrand LJ, van Rooijen MA, Ward D, Leveen P, Xu X, ten Dijke P, Mummery CL, Karlsson S (2001) Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice. EMBO J 20(7):1663–1673PubMedPubMedCentralCrossRefGoogle Scholar
  87. Lauvrud AT, Kelk P, Wiberg M, Kingham PJ (2017) Characterization of human adipose tissue-derived stem cells with enhanced angiogenic and adipogenic properties. J Tissue Eng Regen Med 11(9):2490–2502PubMedPubMedCentralCrossRefGoogle Scholar
  88. Lebrin F, Srun S, Raymond K, Martin S, van den Brink S, Freitas C, Breant C, Mathivet T, Larrivee B, Thomas JL et al (2010) Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nat Med 16(4):420–428PubMedPubMedCentralCrossRefGoogle Scholar
  89. Leveen P, Pekny M, Gebre-Medhin S, Swolin B, Larsson E, Betsholtz C (1994) Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. Genes Dev 8(16):1875–1887CrossRefPubMedGoogle Scholar
  90. Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, Boak BB, Wendel DP (1999) Defective angiogenesis in mice lacking endoglin. Science 284(5419):1534–1537CrossRefPubMedPubMedCentralGoogle Scholar
  91. Li J, Zhang YP, Kirsner RS (2003) Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. Microsc Res Tech 60(1):107–114CrossRefPubMedGoogle Scholar
  92. Lin SL, Kisseleva T, Brenner DA, Duffield JS (2008) Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. Am J Pathol 173(6):1617–1627PubMedPubMedCentralCrossRefGoogle Scholar
  93. Lindahl P, Johansson BR, Leveen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277(5323):242–245CrossRefPubMedGoogle Scholar
  94. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N et al (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277(5322):55–60CrossRefGoogle Scholar
  95. Majesky MW (2007) Developmental basis of vascular smooth muscle diversity. Arterioscler Thromb Vasc Biol 27(6):1248–1258CrossRefPubMedGoogle Scholar
  96. Majesky MW, Dong XR, Regan JN, Hoglund VJ (2011) Vascular smooth muscle progenitor cells: building and repairing blood vessels. Circ Res 108(3):365–377PubMedPubMedCentralCrossRefGoogle Scholar
  97. Mandarino LJ, Sundarraj N, Finlayson J, Hassell HR (1993) Regulation of fibronectin and laminin synthesis by retinal capillary endothelial cells and pericytes in vitro. Exp Eye Res 57(5):609–621CrossRefPubMedGoogle Scholar
  98. Marra F, Choudhury GG, Pinzani M, Abboud HE (1994) Regulation of platelet-derived growth factor secretion and gene expression in human liver fat-storing cells. Gastroenterology 107(4):1110–1117CrossRefPubMedGoogle Scholar
  99. Maxwell PH, Osmond MK, Pugh CW, Heryet A, Nicholls LG, Tan CC, Doe BG, Ferguson DJ, Johnson MH, Ratcliffe PJ (1993) Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int 44(5):1149–1162PubMedCrossRefGoogle Scholar
  100. Mendel TA, Clabough EB, Kao DS, Demidova-Rice TN, Durham JT, Zotter BC, Seaman SA, Cronk SM, Rakoczy EP, Katz AJ et al (2013) Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy. PLoS One 8(5):e65691PubMedPubMedCentralCrossRefGoogle Scholar
  101. Mikawa T, Gourdie RG (1996) Pericardial mesoderm generates a population of coronary smooth muscle cells migrating into the heart along with ingrowth of the epicardial organ. Dev Biol 174(2):221–232PubMedCrossRefGoogle Scholar
  102. Miller FN, Sims DE, Schuschke DA, Abney DL (1992) Differentiation of light-dye effects in the microcirculation. Microvasc Res 44(2):166–184PubMedCrossRefGoogle Scholar
  103. Mills SJ, Cowin AJ, Kaur P (2013) Pericytes, mesenchymal stem cells and the wound healing process. Cells 2(3):621–634PubMedPubMedCentralCrossRefGoogle Scholar
  104. Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A (2008) Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 3(3):265–278PubMedPubMedCentralCrossRefGoogle Scholar
  105. Mohle R, Green D, Moore MA, Nachman RL, Rafii S (1997) Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci U S A 94(2):663–668PubMedPubMedCentralCrossRefGoogle Scholar
  106. Montiel-Eulefi E, Nery AA, Rodrigues LC, Sanchez R, Romero F, Ulrich H (2012) Neural differentiation of rat aorta pericyte cells. Cytometry A 81(1):65–71PubMedCrossRefGoogle Scholar
  107. Nakagawa S, Deli MA, Nakao S, Honda M, Hayashi K, Nakaoke R, Kataoka Y, Niwa M (2007) Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. Cell Mol Neurobiol 27(6):687–694PubMedCrossRefGoogle Scholar
  108. Nakamura K, Kamouchi M, Kitazono T, Kuroda J, Matsuo R, Hagiwara N, Ishikawa E, Ooboshi H, Ibayashi S, Iida M (2008) Role of NHE1 in calcium signaling and cell proliferation in human CNS pericytes. Am J Physiol Heart Circ Physiol 294(4):H1700–H1707PubMedCrossRefGoogle Scholar
  109. Nehls V, Drenckhahn D (1991) Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin. J Cell Biol 113(1):147–154PubMedPubMedCentralCrossRefGoogle Scholar
  110. Obara N, Suzuki N, Kim K, Nagasawa T, Imagawa S, Yamamoto M (2008) Repression via the GATA box is essential for tissue-specific erythropoietin gene expression. Blood 111(10):5223–5232PubMedPubMedCentralCrossRefGoogle Scholar
  111. Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S et al (2000) Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A 97(6):2626–2631PubMedPubMedCentralCrossRefGoogle Scholar
  112. Olson LE, Soriano P (2011) PDGFRbeta signaling regulates mural cell plasticity and inhibits fat development. Dev Cell 20(6):815–826PubMedPubMedCentralCrossRefGoogle Scholar
  113. Oshima M, Oshima H, Taketo MM (1996) TGF-beta receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Dev Biol 179(1):297–302PubMedPubMedCentralCrossRefGoogle Scholar
  114. Ota T, Fujii M, Sugizaki T, Ishii M, Miyazawa K, Aburatani H, Miyazono K (2002) Targets of transcriptional regulation by two distinct type I receptors for transforming growth factor-beta in human umbilical vein endothelial cells. J Cell Physiol 193(3):299–318PubMedPubMedCentralCrossRefGoogle Scholar
  115. Paquet-Fifield S, Schluter H, Li A, Aitken T, Gangatirkar P, Blashki D, Koelmeyer R, Pouliot N, Palatsides M, Ellis S et al (2009) A role for pericytes as microenvironmental regulators of human skin tissue regeneration. J Clin Invest 119(9):2795–2806PubMedPubMedCentralGoogle Scholar
  116. Park TS, Gavina M, Chen CW, Sun B, Teng PN, Huard J, Deasy BM, Zimmerlin L, Peault B (2011) Placental perivascular cells for human muscle regeneration. Stem Cells Dev 20(3):451–463PubMedPubMedCentralCrossRefGoogle Scholar
  117. Popescu FC, Busuioc CJ, Mogosanu GD, Pop OT, Parvanescu H, Lascar I, Nicolae CI, Mogoanta L (2011) Pericytes and myofibroblasts reaction in experimental thermal third degree skin burns. Romanian J Morphol Embryol 52(3 Suppl):1011–1017Google Scholar
  118. Proebstl D, Voisin MB, Woodfin A, Whiteford J, D’Acquisto F, Jones GE, Rowe D, Nourshargh S (2012) Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med 209(6):1219–1234PubMedPubMedCentralCrossRefGoogle Scholar
  119. Que J, Wilm B, Hasegawa H, Wang F, Bader D, Hogan BL (2008) Mesothelium contributes to vascular smooth muscle and mesenchyme during lung development. Proc Natl Acad Sci U S A 105(43):16626–16630PubMedPubMedCentralCrossRefGoogle Scholar
  120. Rajantie I, Ilmonen M, Alminaite A, Ozerdem U, Alitalo K, Salven P (2004) Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells. Blood 104(7):2084–2086PubMedPubMedCentralCrossRefGoogle Scholar
  121. Rajkumar VS, Shiwen X, Bostrom M, Leoni P, Muddle J, Ivarsson M, Gerdin B, Denton CP, Bou-Gharios G, Black CM et al (2006) Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing. Am J Pathol 169(6):2254–2265PubMedPubMedCentralCrossRefGoogle Scholar
  122. Risau W, Engelhardt B, Wekerle H (1990) Immune function of the blood-brain barrier: incomplete presentation of protein (auto-)antigens by rat brain microvascular endothelium in vitro. J Cell Biol 110(5):1757–1766PubMedPubMedCentralCrossRefGoogle Scholar
  123. Rucker HK, Wynder HJ, Thomas WE (2000) Cellular mechanisms of CNS pericytes. Brain Res Bull 51(5):363–369PubMedPubMedCentralCrossRefGoogle Scholar
  124. Sato Y, Rifkin DB (1989) Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. J Cell Biol 109(1):309–315PubMedPubMedCentralCrossRefGoogle Scholar
  125. Sato M, Suzuki S, Senoo H (2003) Hepatic stellate cells: unique characteristics in cell biology and phenotype. Cell Struct Funct 28(2):105–112PubMedPubMedCentralCrossRefGoogle Scholar
  126. Shen Q, Wang Y, Kokovay E, Lin G, Chuang SM, Goderie SK, Roysam B, Temple S (2008) Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 3(3):289–300PubMedPubMedCentralCrossRefGoogle Scholar
  127. Shepro D, Morel NM (1993) Pericyte physiology. FASEB J 7(11):1031–1038PubMedPubMedCentralCrossRefGoogle Scholar
  128. Shimizu F, Sano Y, Maeda T, Abe MA, Nakayama H, Takahashi R, Ueda M, Ohtsuki S, Terasaki T, Obinata M et al (2008) Peripheral nerve pericytes originating from the blood-nerve barrier expresses tight junctional molecules and transporters as barrier-forming cells. J Cell Physiol 217(2):388–399PubMedPubMedCentralCrossRefGoogle Scholar
  129. Sims DE (1986) The pericyte–a review. Tissue Cell 18(2):153–174PubMedPubMedCentralCrossRefGoogle Scholar
  130. Sims DE (1991) Recent advances in pericyte biology–implications for health and disease. Can J Cardiol 7(10):431–443PubMedGoogle Scholar
  131. Sims DE (2000) Diversity within pericytes. Clin Exp Pharmacol Physiol 27(10):842–846.CrossRefPubMedGoogle Scholar
  132. Sims DE, Miller FN, Horne MM, Edwards MJ (1994) Interleukin-2 alters the positions of capillary and venule pericytes in rat cremaster muscle. J Submicrosc Cytol Pathol 26(4):507–513PubMedGoogle Scholar
  133. Soriano P (1994) Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice. Genes Dev 8(16):1888–1896CrossRefPubMedGoogle Scholar
  134. Suematsu M, Aiso S (2001) Professor Toshio Ito: a clairvoyant in pericyte biology. Keio J Med 50(2):66–71CrossRefPubMedGoogle Scholar
  135. Sundberg C, Ljungstrom M, Lindmark G, Gerdin B, Rubin K (1993) Microvascular pericytes express platelet-derived growth factor-beta receptors in human healing wounds and colorectal adenocarcinoma. Am J Pathol 143(5):1377–1388PubMedPubMedCentralGoogle Scholar
  136. Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, Garcia-Verdugo JM, Doetsch F (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3(3):279–288CrossRefPubMedGoogle Scholar
  137. Thomas WE (1999) Brain macrophages: on the role of pericytes and perivascular cells. Brain Res Rev 31(1):42–57CrossRefPubMedGoogle Scholar
  138. Tilton RG, Kilo C, Williamson JR (1979) Pericyte-endothelial relationships in cardiac and skeletal muscle capillaries. Microvasc Res 18(3):325–335CrossRefPubMedGoogle Scholar
  139. Tonnesen MG, Feng X, Clark RA (2000) Angiogenesis in wound healing. J Investig Dermatol Symp Proc 5(1):40–46CrossRefPubMedGoogle Scholar
  140. Tu Z, Li Y, Smith DS, Sheibani N, Huang S, Kern T, Lin F (2011) Retinal pericytes inhibit activated T cell proliferation. Invest Ophthalmol Vis Sci 52(12):9005–9010PubMedPubMedCentralCrossRefGoogle Scholar
  141. Urness LD, Sorensen LK, Li DY (2000) Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nat Genet 26(3):328–331CrossRefPubMedGoogle Scholar
  142. Verbeek MM, Westphal JR, Ruiter DJ, de Waal RM (1995) T lymphocyte adhesion to human brain pericytes is mediated via very late antigen-4/vascular cell adhesion molecule-1 interactions. J Immunol 154(11):5876–5884PubMedGoogle Scholar
  143. Verbeek MM, de Waal RM, Schipper JJ, Van Nostrand WE (1997) Rapid degeneration of cultured human brain pericytes by amyloid beta protein. J Neurochem 68(3):1135–1141CrossRefPubMedGoogle Scholar
  144. Wang S, Voisin MB, Larbi KY, Dangerfield J, Scheiermann C, Tran M, Maxwell PH, Sorokin L, Nourshargh S (2006) Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med 203(6):1519–1532PubMedPubMedCentralCrossRefGoogle Scholar
  145. Wang S, Cao C, Chen Z, Bankaitis V, Tzima E, Sheibani N, Burridge K (2012) Pericytes regulate vascular basement membrane remodeling and govern neutrophil extravasation during inflammation. PLoS One 7(9):e45499PubMedPubMedCentralCrossRefGoogle Scholar
  146. Wessels A, Perez-Pomares JM (2004) The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. Anat Rec A Discov Mol Cell Evol Biol 276(1):43–57CrossRefPubMedGoogle Scholar
  147. Wilm B, Ipenberg A, Hastie ND, Burch JB, Bader DM (2005) The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature. Development 132(23):5317–5328CrossRefPubMedGoogle Scholar
  148. Wong L, Yamasaki G, Johnson RJ, Friedman SL (1994) Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture. J Clin Invest 94(4):1563–1569PubMedPubMedCentralCrossRefGoogle Scholar
  149. Yamashima T, Tonchev AB, Vachkov IH, Popivanova BK, Seki T, Sawamoto K, Okano H (2004) Vascular adventitia generates neuronal progenitors in the monkey hippocampus after ischemia. Hippocampus 14(7):861–875CrossRefPubMedGoogle Scholar
  150. Yamashita J, Itoh H, Hirashima M, Ogawa M, Nishikawa S, Yurugi T, Naito M, Nakao K, Nishikawa S (2000) Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 408(6808):92–96CrossRefPubMedGoogle Scholar
  151. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J (2000) Vascular-specific growth factors and blood vessel formation. Nature 407(6801):242–248CrossRefPubMedGoogle Scholar
  152. Yang X, Castilla LH, Xu X, Li C, Gotay J, Weinstein M, Liu PP, Deng CX (1999) Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development 126(8):1571–1580PubMedPubMedCentralGoogle Scholar
  153. Zhang X, Peault B, Chen W, Li W, Corselli M, James AW, Lee M, Siu RK, Shen P, Zheng Z et al (2011) The Nell-1 growth factor stimulates bone formation by purified human perivascular cells. Tissue Eng Part A 17(19–20):2497–2509PubMedPubMedCentralCrossRefGoogle Scholar
  154. Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR et al (2008) Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454(7200):109–113PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Center of Excellence for Stem Cells and Regenerative MedicineZewail City of Science and TechnologyGizaEgypt

Personalised recommendations