Pericytes in Tissue Engineering

  • Betül Çelebi-SaltikEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1109)


Pericytes have crucial roles in blood-brain barrier function, blood vessel function/stability, angiogenesis, endothelial cell proliferation/differentiation, wound healing, and hematopoietic stem cells maintenance. They can be isolated from fetal and adult tissues and have multipotential differentiation capacity as mesenchymal stem cells (MSCs). All of these properties make pericytes as preferred cells in the field of tissue engineering. Current developments have shown that tissue-engineered three-dimensional (3D) systems including multiple cell layers (or types) and a supporting biological matrix represent the in vivo environment better than those monolayers on plastic dishes. Tissue-engineered models are also more ethical and cheaper systems than animal models. This chapter describes the role of pericytes in tissue engineering for regenerative medicine.


Pericytes Tissue engineering Mesenchymal stem cells Hematopoietic stem cells Niche Scaffold Bone tissue engineering Cartilage tissue engineering Dermal tissue engineering Vascular tissue engineering Cardiac tissue engineering Blood tissue engineering 


Conflict of Interest Statement

The author declares that she has no conflicts of interest concerning this work.

Ethical Approval

This article does not contain any studies with human participants or animals performed by the author.

Informed Consent

This article does not contain any studies with human participants or animals performed by the author.


  1. 1.
    Alakpa EV, Jayawarna V, Burgess KEV, West CC, Peault B, Ulijn RV, Dalby MJ (2017) Improving cartilage phenotype from differentiated pericytes in tunable peptide hydrogels. Sci Rep 7:6895CrossRefGoogle Scholar
  2. 2.
    Andreeva ER, Pugach IM, Gordon D, Orekhov AN (1998) Continuous subendothelial network formed by pericyte-like cells in human vascular bed. Tissue Cell 30:127–135CrossRefGoogle Scholar
  3. 3.
    Attwell D, Mishra A, Hall CN, O'Farrell FM, Dalkara T (2016) What is a pericyte? J Cereb Blood Flow Metab 36:451–455CrossRefGoogle Scholar
  4. 4.
    Avolio E, Alvino VV, Ghorbel MT, Campagnolo P (2017) Perivascular cells and tissue engineering: current applications and untapped potential. Pharmacol Ther 171:83–92CrossRefGoogle Scholar
  5. 5.
    Avolio E, Rodriguez-Arabaolaza I, Spencer HL, Riu F, Mangialardi G, Slater SC, Rowlinson J, Alvino VV, Idowu OO, Soyombo S, Oikawa A, Swim MM, Kong CH, Cheng H, Jia H, Ghorbel MT, Hancox JC, Orchard CH, Angelini G, Emanueli C, Caputo M, Madeddu P (2015) Expansion and characterization of neonatal cardiac pericytes provides a novel cellular option for tissue engineering in congenital heart disease. J Am Heart Assoc 4:e002043CrossRefGoogle Scholar
  6. 6.
    Bhattacharya D, Rossi DJ, Bryder D, Weissman IL (2006) Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies without host conditioning. J Exp Med 203:73–85CrossRefGoogle Scholar
  7. 7.
    Bigas A, Robert-Moreno A, Espinosa L (2010) The notch pathway in the developing hematopoietic system. Int J Dev Biol 54:1175–1188CrossRefGoogle Scholar
  8. 8.
    Blocki A, Wang YT, Koch M, Peh P, Beyer S, Law P, Hui J, Raghunath M (2013) Not all MSCs can act as pericytes: functional in vitro assays to distinguish pericytes from other mesenchymal stem cells in angiogenesis. Stem Cells Dev 22:2347–2355CrossRefGoogle Scholar
  9. 9.
    Bodnar RJ, Satish L, Yates CC, Wells A (2016) Pericytes: a newly recognized player in wound healing. Wound Repair Regen 24:204–214CrossRefGoogle Scholar
  10. 10.
    Campagnolo P, Cesselli D, Al Haj Zen A, Beltrami AP, Krankel N, Katare R, Angelini G, Emanueli C, Madeddu P (2010) Human adult vena saphena contains perivascular progenitor cells endowed with clonogenic and proangiogenic potential. Circulation 121:1735–1745CrossRefGoogle Scholar
  11. 11.
    Caplan AI (2017) New MSC: MSCs as pericytes are sentinels and gatekeepers. J Orthop Res 35:1151–1159CrossRefGoogle Scholar
  12. 12.
    Carneiro TN, Novaes DS, Rabelo RB, Celebi B, Chevallier P, Mantovani D, Beppu MM, Vieira RS (2013) BSA and fibrinogen adsorption on chitosan/kappa-carrageenan polyelectrolyte complexes. Macromol Biosci 13:1072–1083CrossRefGoogle Scholar
  13. 13.
    Celebi B, Cloutier M, Balloni R, Mantovani D, Bandiera A (2012) Human elastin-based recombinant biopolymers improve mesenchymal stem cell differentiation. Macromol Biosci 12:1546–1554CrossRefGoogle Scholar
  14. 14.
    Celebi B, Mantovani D, Pineault N (2011) Effects of extracellular matrix proteins on the growth of haematopoietic progenitor cells. Biomed Mater 6:055011CrossRefGoogle Scholar
  15. 15.
    Celebi B, Mantovani D, Pineault N (2011) Irradiated mesenchymal stem cells improve the ex vivo expansion of hematopoietic progenitors by partly mimicking the bone marrow endosteal environment. J Immunol Methods 370:93–103CrossRefGoogle Scholar
  16. 16.
    Celebi Saltik B, Gokcinar Yagci B (2017) Expansion of human umbilical cord blood hematopoietic progenitors with cord vein pericytes. Turk J Biol 41:49–U265CrossRefGoogle Scholar
  17. 17.
    Celebi Saltik B, Oteyaka MO (2016) Cardiac patch design: compatibility of nanofiber materials prepared by electrospinning method with stem cells. Turk J Biol 40:510–518CrossRefGoogle Scholar
  18. 18.
    Chen CW, Okada M, Proto JD, Gao XQ, Sekiya N, Beckman SA, Corselli M, Crisan M, Saparov A, Tobita K, Peault B, Huard J (2013) Human pericytes for ischemic heart repair. Stem Cells 31:305–316CrossRefGoogle Scholar
  19. 19.
    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 33:557–573CrossRefGoogle Scholar
  20. 20.
    Chin CJ, Li SW, Corselli M, Casero D, Zhu YH, Bin He C, Hardy R, Peault B, Crooks GM (2018) Transcriptionally and functionally distinct mesenchymal subpopulations are generated from human pluripotent stem cells. Stem Cell Rep 10:436–446CrossRefGoogle Scholar
  21. 21.
    Chong MS, Chan J, Choolani M, Lee CN, Teoh SH (2009) Development of cell-selective films for layered co-culturing of vascular progenitor cells. Biomaterials 30:2241–2251CrossRefGoogle Scholar
  22. 22.
    Chung CG, James AW, Asatrian G, Chang L, Nguyen A, Le K, Bayani G, Lee R, Stoker D, Zhang XL, Ting K, Peault B, Soo C (2014) Human perivascular stem cell-based bone graft substitute induces rat spinal fusion. Stem Cells Transl Med 3:1231–1241CrossRefGoogle Scholar
  23. 23.
    Corselli M, Chin CJ, Parekh C, Sahaghian A, Wang W, Ge S, Evseenko D, Wang X, Montelatici E, Lazzari L, Crooks GM, Peault B (2013) Perivascular support of human hematopoietic stem/progenitor cells. Blood 121:2891–2901CrossRefGoogle Scholar
  24. 24.
    Corselli M, Crisan M, Murray IR, West CC, Scholes J, Codrea F, Khan N, Peault B (2013) Identification of perivascular mesenchymal stromal/stem cells by flow cytometry. Cytometry A 83:714–720CrossRefGoogle Scholar
  25. 25.
    Crisan M, Corselli M, Chen CW, Peault B (2011) Multilineage stem cells in the adult A perivascular legacy? Organogenesis 7:101–104CrossRefGoogle Scholar
  26. 26.
    Crisan M, Corselli M, Chen WC, Peault B (2012) Perivascular cells for regenerative medicine. J Cell Mol Med 16:2851–2860CrossRefGoogle Scholar
  27. 27.
    Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313CrossRefGoogle Scholar
  28. 28.
    Dhandayuthapani B, Yoshida Y, Maekawa T, Kumar DS (2011) Polymeric scaffolds in tissue engineering application: a review. Int J Polym Sci 2000:1–19CrossRefGoogle Scholar
  29. 29.
    Dore-Duffy P, Cleary K (2011) Morphology and properties of pericytes. Methods Mol Biol 686:49–68CrossRefGoogle Scholar
  30. 30.
    Dumont N, Boyer L, Emond H, Celebi-Saltik B, Pasha R, Bazin R, Mantovani D, Roy DC, Pineault N (2014) Medium conditioned with mesenchymal stromal cell-derived osteoblasts improves the expansion and engraftment properties of cord blood progenitors. Exp Hematol 42:741–752 e1CrossRefGoogle Scholar
  31. 31.
    Ellison-Hughes GM, Madeddu P (2017) Exploring pericyte and cardiac stem cell secretome unveils new tactics for drug discovery. Pharmacol Ther 171:1–12CrossRefGoogle Scholar
  32. 32.
    Farrington-Rock C, Crofts NJ, Doherty MJ, Ashton BA, Griffin-Jones C, Canfield AE (2004) Chondrogenic and adipogenic potential of microvascular pericytes. Circulation 110:2226–2232CrossRefGoogle Scholar
  33. 33.
    Fuoco C, Sangalli E, Vono R, Testa S, Sacchetti B, Latronico MV, Bernardini S, Madeddu P, Cesareni G, Seliktar D, Rizzi R, Bearzi C, Cannata SM, Spinetti G, Gargioli C (2014) 3D hydrogel environment rejuvenates aged pericytes for skeletal muscle tissue engineering. Front Physiol 5:203CrossRefGoogle Scholar
  34. 34.
    Gokcinar-Yagci B, Ozyuncu O, Celebi-Saltik B (2016) Isolation, characterisation and comparative analysis of human umbilical cord vein perivascular cells and cord blood mesenchymal stem cells. Cell Tissue Bank 17:345–352CrossRefGoogle Scholar
  35. 35.
    Gokcinar-Yagci B, Uckan-Cetinkaya D, Celebi-Saltik B (2015) Pericytes: properties, functions and applications in tissue engineering. Stem Cell Rev 11:549–559CrossRefGoogle Scholar
  36. 36.
    Gokcinar-Yagci B, Yersal N, Korkusuz P, Celebi-Saltik B (2018) Generation of human umbilical cord vein CD146+ perivascular cell origined three-dimensional vascular construct. Microvasc Res 118:101–112CrossRefGoogle Scholar
  37. 37.
    He W, Nieponice A, Soletti L, Hong Y, Gharaibeh B, Crisan M, Usas A, Peault B, Huard J, Wagner WR, Vorp DA (2010) Pericyte-based human tissue engineered vascular grafts. Biomaterials 31:8235–8244CrossRefGoogle Scholar
  38. 38.
    Hindle P, Khan N, Biant L, Peault B (2017) The infrapatellar fat pad as a source of perivascular stem cells with increased chondrogenic potential for regenerative medicine. Stem Cells Transl Med 6:77–87CrossRefGoogle Scholar
  39. 39.
    Hoshiba T, Lu HX, Kawazoe N, Chen GP (2010) Decellularized matrices for tissue engineering. Expert Opin Biol Ther 10:1717–1728CrossRefGoogle Scholar
  40. 40.
    Howard D, Buttery LD, Shakesheff KM, Roberts SJ (2008) Tissue engineering: strategies, stem cells and scaffolds. J Anat 213:66–72CrossRefGoogle Scholar
  41. 41.
    Isakson M, de Blacam C, Whelan D, McArdle A, Clover AJ (2015) Mesenchymal stem cells and cutaneous wound healing: current evidence and future potential. Stem Cells Int 2015:831095CrossRefGoogle Scholar
  42. 42.
    James AW, Hindle P, Murray IR, West CC, Tawonsawatruk T, Shen J, Asatrian G, Zhang X, Nguyen V, Simpson AH, Ting K, Peault B, Soo C (2017) Pericytes for the treatment of orthopedic conditions. Pharmacol Ther 171:93–103CrossRefGoogle Scholar
  43. 43.
    James AW, Zara JN, Corselli M, Askarinam A, Zhou AM, Hourfar A, Nguyen A, Megerdichian S, Asatrian G, Pang S, Stoker D, Zhang X, Wu B, Ting K, Peault B, Soo C (2012) An abundant perivascular source of stem cells for bone tissue engineering. Stem Cells Transl Med 1:673–684CrossRefGoogle Scholar
  44. 44.
    Kannan RY, Salacinski HJ, Butler PE, Hamilton G, Seifalian AM (2005) Current status of prosthetic bypass grafts: a review. J Biomed Mater Res B Appl Biomater 74:570–581CrossRefGoogle Scholar
  45. 45.
    Katare R, Riu F, Mitchell K, Gubernator M, Campagnolo P, Cui YX, Fortunato O, Avolio E, Cesselli D, Beltrami AP, Angelini G, Emanueli C, Madeddu P (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 109:894–U191CrossRefGoogle Scholar
  46. 46.
    Koch AE, Kronfeldharrington LB, Szekanecz Z, Cho MM, Haines GK, Harlow LA, Strieter RM, Kunkel SL, Massa MC, Barr WG, Jimenez SA (1993) In-situ expression of cytokines and cellular adhesion molecules in the skin of patients with systemic-sclerosis – their role in early and late disease. Pathobiology 61:239–246CrossRefGoogle Scholar
  47. 47.
    McDonald AG, Yang K, Roberts HR, Monroe DM, Hoffman M (2008) Perivascular tissue factor is down-regulated following cutaneous wounding: implications for bleeding in hemophilia. Blood 111:2046–2048CrossRefGoogle Scholar
  48. 48.
    Mills SJ, Cowin AJ, Kaur P (2013) Pericytes, mesenchymal stem cells and the wound healing process. Cell 2:621–634CrossRefGoogle Scholar
  49. 49.
    Mravic M, Asatrian G, Soo C, Lugassy C, Barnhill RL, Dry SM, Peault B, James AW (2014) From pericytes to perivascular tumours: correlation between pathology, stem cell biology, and tissue engineering. Int Orthop 38:1819–1824CrossRefGoogle Scholar
  50. 50.
    Murphy CM, O'Brien FJ, Little DG, Schindeler A (2013) Cell-scaffold interactions in the bone tissue engineering triad. Eur Cell Mater 26:120–132CrossRefGoogle Scholar
  51. 51.
    Nees S, Weiss DR, Senftl A, Knott M, Forch S, Schnurr M, Weyrich P, Juchem G (2012) Isolation, bulk cultivation, and characterization of coronary microvascular pericytes: the second most frequent myocardial cell type in vitro. Am J Physiol Heart Circ Physiol 302:H69–H84CrossRefGoogle Scholar
  52. 52.
    Nerem RM (1992) Tissue engineering in the USA. Med Biol Eng Comput 30:CE8–C12CrossRefGoogle Scholar
  53. 53.
    Pang YWY, Feng JF, Daltoe F, Fatscher R, Gentleman E, Gentleman MM, Sharpe PT (2016) Perivascular stem cells at the tip of mouse incisors regulate tissue regeneration. J Bone Miner Res 31:514–523CrossRefGoogle Scholar
  54. 54.
    Paquet-Fifield S, Schluter H, Li A, Aitken T, Gangatirkar P, Blashki D, Koelmeyer R, Pouliot N, Palatsides M, Ellis S, Brouard N, Zannettino A, Saunders N, Thompson N, Li J, Kaur P (2009) A role for pericytes as microenvironmental regulators of human skin tissue regeneration. J Clin Investig 119:2795–2806PubMedGoogle Scholar
  55. 55.
    Place ES, George JH, Williams CK, Stevens MM (2009) Synthetic polymer scaffolds for tissue engineering. Chem Soc Rev 38:1139–1151CrossRefGoogle Scholar
  56. 56.
    Rajkumar VS, Shiwen X, Bostrom M, Leoni P, Muddle J, Ivarsson M, Gerdin B, Denton CP, Bou-Gharios G, Black CM, Abraham DJ (2006) Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing. Am J Pathol 169:2254–2265CrossRefGoogle Scholar
  57. 57.
    Scadden DT (2006) The stem-cell niche as an entity of action. Nature 441:1075–1079CrossRefGoogle Scholar
  58. 58.
    Stark K, Eckart A, Haidari S, Tirniceriu A, Lorenz M, von Bruhl ML, Gartner F, Khandoga AG, Legate KR, Pless R, Hepper I, Lauber K, Walzog B, Massberg S (2013) Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and ‘instruct’ them with pattern-recognition and motility programs. Nat Immunol 14:41–51CrossRefGoogle Scholar
  59. 59.
    Tawonsawatruk T, West CC, Murray IR, Soo C, Peault B, Simpson AH (2016) Adipose derived pericytes rescue fractures from a failure of healing – non-union. Sci Rep 6:22779CrossRefGoogle Scholar
  60. 60.
    van der Meer AD, Orlova VV, ten Dijke P, van den Berg A, Mummery CL (2013) Three-dimensional co-cultures of human endothelial cells and embryonic stem cell-derived pericytes inside a microfluidic device. Lab Chip 13:3562–3568CrossRefGoogle Scholar
  61. 61.
    Wendel JS, Ye L, Tao R, Zhang J, Zhang J, Kamp TJ, Tranquillo RT (2015) Functional effects of a tissue-engineered cardiac patch from human induced pluripotent stem cell-derived cardiomyocytes in a rat infarct model. Stem Cells Transl Med 4:1324–1332CrossRefGoogle Scholar
  62. 62.
    Wu YX, Jing XZ, Sun Y, Ye YP, Guo JC, Huang JM, Xiang W, Zhang JM, Guo FJ (2017) CD146+ skeletal stem cells from growth plate exhibit specific chondrogenic differentiation capacity in vitro. Mol Med Rep 16:8019–8028CrossRefGoogle Scholar
  63. 63.
    Xu JG, Gong T, Heng BC, Zhang CF (2017) A systematic review: differentiation of stem cells into functional pericytes. FASEB J 31:1775–1786CrossRefGoogle Scholar
  64. 64.
    Zamora DO, Natesan S, Becerra S, Wrice N, Chung E, Suggs LJ, Christy RJ (2013) Enhanced wound vascularization using a dsASCs seeded FPEG scaffold. Angiogenesis 16:745–757CrossRefGoogle Scholar
  65. 65.
    Zebardast N, Lickorish D, Davies JE (2010) Human umbilical cord perivascular cells (HUCPVC): a mesenchymal cell source for dermal wound healing. Organogenesis 6:197–203CrossRefGoogle Scholar
  66. 66.
    Zhang S, Ba K, Wu L, Lee S, Peault B, Petrigliano FA, McAllister DR, Adams JS, Evseenko D, Lin Y (2015) Adventitial cells and perictyes support chondrogenesis through different mechanisms in 3-dimensional cultures with or without nanoscaffolds. J Biomed Nanotechnol 11:1799–1807CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Stem Cell SciencesHacettepe University Graduate School of Health SciencesAnkaraTurkey
  2. 2.Center for Stem Cell Research and DevelopmentHacettepe UniversityAnkaraTurkey

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