Skip to main content
SpringerLink
Log in

Pericytes in Veterinary Species: Prospective Isolation, Characterization and Tissue Regeneration Potential

  • Chapter
  • First Online:
Pericyte Biology - Novel Concepts

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1109))

Abstract

Although pericytes have long been known for their roles in blood vessel regulation, it was not until a decade ago that their tissue regeneration potential began to be considered, after studies showed that pericytes were the in vivo counterparts of mesenchymal stem/stromal cells (MSCs). The prospective isolation and culture expansion of pericytes brought great excitement as it opened the way to the therapeutic use of well-defined cell populations with known regenerative potential to overcome concerns associated with the use of traditional MSC preparations. Studies first in humans and later in the horse and other domestic species showed that indeed cultured pericytes had key characteristics of MSCs, namely, their immunophenotype and the abilities to grow clonally and to differentiate into mature mesenchymal cells both in vitro and vivo. Several studies with human pericytes, and to a much lesser extent with animal pericytes, have also shown significant promise in tissue repair in different disease models. This review summarizes current knowledge on the tissue regeneration properties of pericytes from domestic animals and outlines future steps necessary for realizing their full potential both in clinical veterinary medicine and in preclinical testing of human therapies using large animal models, including the need for robust approaches for isolation, culture and appropriate in vivo testing of the tissue regenerative properties of pericytes in these species.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Alcayaga-Miranda F, Cuenca J, Khoury M (2017) Antimicrobial activity of mesenchymal stem cells: current status and new perspectives of antimicrobial peptide-based therapies. Front Immunol 8:339

    Article  Google Scholar 

  2. Alvino VV, Fernández-Jiménez R, Rodriguez-Arabaolaza I et al (2018) Transplantation of allogeneic pericytes improves myocardial vascularization and reduces interstitial fibrosis in a swine model of reperfused acute myocardial infarction. J Am Heart Assoc 7(2): e006727

    Google Scholar 

  3. Andreeva E, Bobyleva P, Gornostaeva A et al (2017) Interaction of multipotent mesenchymal stromal and immune cells: bidirectional effects. Cytotherapy 19:1152–1166

    Article  CAS  Google Scholar 

  4. Armulik A, Genove G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21:193–215

    Article  CAS  Google Scholar 

  5. Barrachina L, Remacha AR, Romero A et al (2016) Effect of inflammatory environment on equine bone marrow derived mesenchymal stem cells immunogenicity and immunomodulatory properties. Vet Immunol Immunopathol 171:57–65

    Article  CAS  Google Scholar 

  6. Basini G, Falasconi I, Bussolati S et al (2014) Isolation of endothelial cells and pericytes from swine corpus luteum. Domest Anim Endocrinol 48:100–109

    Article  CAS  Google Scholar 

  7. Bobrie A, Colombo M, Raposo G et al (2011) Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12:1659–1668

    Article  CAS  Google Scholar 

  8. Bourin P, Bunnell BA, Casteilla L et al (2013) Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 15:641–648

    Article  Google Scholar 

  9. Brehm W, Burk J, Delling U (2014) Application of stem cells for the treatment of joint disease in horses. Methods Mol Biol 1213:215–228

    Article  Google Scholar 

  10. Burk J, Badylak SF, Kelly J et al (2013) Equine cellular therapy – from stall to bench to bedside? Cytometry A 83:103–113

    Article  Google Scholar 

  11. Caplan AI (2008) All MSCs are pericytes? Cell Stem Cell 3:229–230

    Article  CAS  Google Scholar 

  12. Caplan Arnold I, Correa D (2011) The MSC: an injury drugstore. Cell Stem Cell 9:11–15

    Article  CAS  Google Scholar 

  13. Chen CW, Okada M, Proto JD et al (2013) Human pericytes for ischemic heart repair. Stem Cells 31:305–316

    Article  CAS  Google Scholar 

  14. Chen WC, Peault B, Huard J (2015) Regenerative translation of human blood-vessel-derived MSC precursors. Stem Cells Int 2015:375187

    PubMed  PubMed Central  Google Scholar 

  15. Corradetti B, Lange-Consiglio A, Barucca M et al (2011) Size-sieved subpopulations of mesenchymal stem cells from intervascular and perivascular equine umbilical cord matrix. Cell Prolif 44:330–342

    Article  CAS  Google Scholar 

  16. Corselli M, Chen CW, Sun B et al (2012) The tunica adventitia of human arteries and veins as a source of mesenchymal stem cells. Stem Cells Dev 21:1299–1308

    Article  CAS  Google Scholar 

  17. Cortés-Araya Y, Amilon K, Rink BE et al (2018) Comparison of antibacterial and immunological properties of mesenchymal stem/stromal cells from equine bone marrow, endometrium and adipose tissue. Stem Cells Dev https://doi.org/10.1089/scd.2017.0241

  18. Crisan M, Corselli M, Chen WCW et al (2012) Perivascular cells for regenerative medicine. J Cell Mol Med 16:2851–2860

    Article  CAS  Google Scholar 

  19. Crisan M, Yap S, Casteilla L et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313

    Article  CAS  Google Scholar 

  20. De Schauwer C, Goossens K, Piepers S et al (2014) Characterization and profiling of immunomodulatory genes of equine mesenchymal stromal cells from non-invasive sources. Stem Cell Res Ther 5:6

    Article  Google Scholar 

  21. De Schauwer C, Meyer E, Van De Walle GR et al (2011) Markers of stemness in equine mesenchymal stem cells: a plea for uniformity. Theriogenology 75(8):1431–1443

    Article  Google Scholar 

  22. Dellavalle A, Maroli G, Covarello D et al (2011) Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells. Nat Commun 2:499

    Article  CAS  Google Scholar 

  23. Dellavalle A, Sampaolesi M, Tonlorenzi R et al (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol 9:255–267

    Article  CAS  Google Scholar 

  24. Demoulin J-B, Montano-Almendras CP (2012) Platelet-derived growth factors and their receptors in normal and malignant hematopoiesis. Am J Blood Res 2:44–56

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Dominici M, Blanc K, Mueller I (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317

    Article  CAS  Google Scholar 

  26. Donadeu FX, Esteves CL (2015) Prospects and challenges of induced pluripotent stem cells in equine health. Front Vet Sci 2:59

    Article  Google Scholar 

  27. Eliasberg CD, Dar A, Jensen AR et al (2017) Perivascular stem cells diminish muscle atrophy following massive rotator cuff tears in a small animal model. J Bone Joint Surg Am 99:331–341

    Article  Google Scholar 

  28. Esteves CL, Donadeu FX (2018) Pericytes and their potential in regenerative medicine across species. Cytometry A 93(1):50–59

    Article  CAS  Google Scholar 

  29. Esteves CL, Sheldrake TA, Dawson L et al (2017) Equine mesenchymal stromal cells retain a pericyte-like phenotype. Stem Cells Dev 26:964–972

    Article  CAS  Google Scholar 

  30. Esteves CL, Sheldrake TA, Mesquita SP et al (2017) Isolation and characterization of equine native MSC populations. Stem Cell Res Ther 8:80

    Article  Google Scholar 

  31. Feng J, Mantesso A, De Bari C et al (2011) Dual origin of mesenchymal stem cells contributing to organ growth and repair. Proc Natl Acad Sci U S A 108:6503–6508

    Article  CAS  Google Scholar 

  32. Fortier LA, Travis AJ (2011) Stem cells in veterinary medicine. Stem Cell Res Ther 2:9

    Article  Google Scholar 

  33. Fuoco C, Sangalli E, Vono R et al (2014) 3D hydrogel environment rejuvenates aged pericytes for skeletal muscle tissue engineering. Front Physiol 5:203

    Article  Google Scholar 

  34. Gugjoo MB, Amarpal, Chandra V et al (2018) Mesenchymal stem cell research in veterinary medicine. Curr Stem Cell Res Ther 13(8):645–657

    Google Scholar 

  35. Harman RM, Yang S, He MK et al (2017) Antimicrobial peptides secreted by equine mesenchymal stromal cells inhibit the growth of bacteria commonly found in skin wounds. Stem Cell Res Ther 8:157

    Article  Google Scholar 

  36. He W, Nieponice A, Soletti L et al (2010) Pericyte-based human tissue engineered vascular grafts. Biomaterials 31:8235–8244

    Article  CAS  Google Scholar 

  37. Hindle P, Baily JE, Khan N et al (2016) Perivascular mesenchymal stem cells in sheep: characterisation and autologous transplantation in a model of articular cartilage repair. Stem Cells Dev 25(21):1659–1669

    Article  CAS  Google Scholar 

  38. James AW, Zhang X, Crisan M et al (2017) Isolation and characterization of canine perivascular stem/stromal cells for bone tissue engineering. PLoS One 12:e0177308

    Article  Google Scholar 

  39. Johnson V, Webb T, Norman A et al (2017) Activated mesenchymal stem cells interact with antibiotics and host innate immune responses to control chronic bacterial infections. Sci Rep 7:9575

    Article  Google Scholar 

  40. Kisiel AH, Mcduffee LA, Masaoud E et al (2012) Isolation, characterization, and in vitro proliferation of canine mesenchymal stem cells derived from bone marrow, adipose tissue, muscle, and periosteum. Am J Vet Res 73:1305–1317

    Article  CAS  Google Scholar 

  41. Konig MA, Canepa DD, Cadosch D et al (2016) Direct transplantation of native pericytes from adipose tissue: a new perspective to stimulate healing in critical size bone defects. Cytotherapy 18:41–52

    Article  Google Scholar 

  42. Krautler NJ, Kana V, Kranich J et al (2012) Follicular dendritic cells emerge from ubiquitous perivascular precursors. Cell 150:194–206

    Article  CAS  Google Scholar 

  43. Lacitignola L, Crovace A, Rossi G et al (2008) Cell therapy for tendinitis, experimental and clinical report. Vet Res Commun 32:S33–S38

    Article  Google Scholar 

  44. Lauvrud AT, Kelk P, Wiberg M et al (2017) Characterization of human adipose tissue-derived stem cells with enhanced angiogenic and adipogenic properties. J Tissue Eng Regen Med 11(9):2490–2502

    Article  CAS  Google Scholar 

  45. Le Blanc K, Davies LC (2015) Mesenchymal stromal cells and the innate immune response. Immunol Lett 168:140–146

    Article  Google Scholar 

  46. Lovati A, Corradetti B, Lange C et al (2011) Comparison of equine bone marrow-, umbilical cord matrix and amniotic fluid-derived progenitor cells. Vet Res Commun 35:103–121

    Article  Google Scholar 

  47. Mendicino M, Bailey A, Wonnacott K et al (2014) MSC-based product characterization for clinical trials: an FDA perspective. Cell Stem Cell 14:141–145

    Article  CAS  Google Scholar 

  48. Park TS, Gavina M, Chen CW et al (2011) Placental perivascular cells for human muscle regeneration. Stem Cells Dev 20:451–463

    Article  CAS  Google Scholar 

  49. Pevsner-Fischer M, Levin S, Zipori D (2011) The origins of mesenchymal stromal cell heterogeneity. Stem Cell Rev 7:560–568

    Article  CAS  Google Scholar 

  50. Ranera B, Antczak D, Miller D et al (2015) Donor-derived equine mesenchymal stem cells suppress proliferation of mismatched lymphocytes. Equine Vet J 48:253–260

    Article  Google Scholar 

  51. Ranera B, Barry F (2014) A horse of a different color. Cytometry A 85:658–659

    Article  Google Scholar 

  52. Ranera B, Lyahyaia J, Romero A et al (2011) Immunophenotype and gene expression profiles of cell surface markers of mesenchymal stem cells derived from equine bone marrow and adipose tissue. Vet Immunol Immunopathol 144:147–154

    Article  CAS  Google Scholar 

  53. Remacha AR, Barrachina L, Alvarez-Arguedas S et al (2015) Expression of genes involved in immune response and in vitro immunosuppressive effect of equine MSCs. Vet Immunol Immunopathol 165:107–118

    Article  CAS  Google Scholar 

  54. Rink BE, Amilon KR, Esteves CL et al (2017) Isolation and characterization of equine endometrial mesenchymal stromal cells. Stem Cell Res Ther 8:166

    Article  Google Scholar 

  55. Rink E, Teresa B, French H et al (2018) The fate of autologous endometrial mesenchymal stromal cells after application in the healthy equine uterus. Stem Cells Dev 27:1046–1052 0:null

    Article  CAS  Google Scholar 

  56. Sacchetti B, Funari A, Michienzi S et al (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336

    Article  CAS  Google Scholar 

  57. Schnabel LV, Fortier LA, Mcilwraith CW et al (2013) Therapeutic use of stem cells in horses: which type, how, and when? Vet J 197:570–577

    Article  Google Scholar 

  58. Shi Y, Su J, Roberts AI et al (2012) How mesenchymal stem cells interact with tissue immune responses. Trends Immunol 33:136–143

    Article  CAS  Google Scholar 

  59. Sims DE (1986) The pericyte – a review. Tissue Cell 18:153–174

    Article  CAS  Google Scholar 

  60. Skrahin A, Ahmed RK, Ferrara G et al (2014) Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial. Lancet Respir Med 2:108–122

    Article  Google Scholar 

  61. Smith AN, Willis E, Chan VT et al (2010) Mesenchymal stem cells induce dermal fibroblast responses to injury. Exp Cell Res 316:48–54

    Article  CAS  Google Scholar 

  62. Spaas J, De Schauwer C, Cornillie P et al (2013) Culture and characterisation of equine peripheral blood mesenchymal stromal cells. Vet J 195:107–113

    Article  CAS  Google Scholar 

  63. Spitzer TLB, Rojas A, Zelenko Z et al (2012) Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype. Biol Reprod 86(58):51–16

    Google Scholar 

  64. Tang W, Zeve D, Suh JM et al (2008) White fat progenitor cells reside in the adipose vasculature. Science 322:583–586

    Article  CAS  Google Scholar 

  65. Taylor SE, Smith RK, Clegg PD (2007) Mesenchymal stem cell therapy in equine musculoskeletal disease: scientific fact or clinical fiction? Equine Vet J 39:172–180

    Article  CAS  Google Scholar 

  66. Tessier L, Bienzle D, Williams LB et al (2015) Phenotypic and immunomodulatory properties of equine cord blood-derived mesenchymal stromal cells. PLoS One 10:e0122954

    Article  Google Scholar 

  67. Van Dijk CG, Nieuweboer FE, Pei JY et al (2015) The complex mural cell: pericyte function in health and disease. Int J Cardiol 190:75–89

    Article  Google Scholar 

  68. Vezina AR, Lavoie-Lamoureux A, Lavoie JP et al (2013) Inflammatory stimuli differentially modulate the transcription of paracrine signaling molecules of equine bone marrow multipotent mesenchymal stromal cells. Osteoarthr Cartil 21:1116–1124

    Article  Google Scholar 

  69. Wilson JG, Liu KD, Zhuo H et al (2015) Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med 3:24–32

    Article  Google Scholar 

  70. Wu CC, Liu FL, Sytwu HK et al (2016) CD146+ mesenchymal stem cells display greater therapeutic potential than CD146- cells for treating collagen-induced arthritis in mice. Stem Cell Res Ther 7:23

    Article  Google Scholar 

  71. Youn SW, Jung K-H, Chu K et al (2015) Feasibility and safety of intra-arterial pericyte progenitor cell delivery following mannitol-induced transient blood brain barrier opening in a canine model. Cell Transplant 24:1469–1479

    Article  Google Scholar 

  72. Zimmerlin L, Donnenberg VS, Pfeifer ME et al (2010) Stromal vascular progenitors in adult human adipose tissue. Cytometry A 77:22–30

    PubMed  PubMed Central  Google Scholar 

  73. Zimmerlin L, Donnenberg VS, Rubin JP et al (2013) Mesenchymal markers on human adipose stem/progenitor cells. Cytometry A 83:134–140

    Article  Google Scholar 

  74. Zumla A, Rao M, Wallis RS et al (2016) Host-directed therapies for infectious diseases: current status, recent progress, and future prospects. Lancet Infect Dis 16:e47–e63

    Article  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the Horserace Betting Levy Board (Prj768 awarded to FXD, and SPrj022 to CLE and FXD) and the Petplan Charitable Trust (2017-568-606 awarded to CLE and FXD) for funding. FXD received Institute Strategic Programme Grant funding from the Biotechnology and Biological Sciences Research Council. The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Developmental Biology, The Roslin Institute, University of Edinburgh, Edinburgh, UK

    Cristina L. Esteves & F. Xavier Donadeu

  2. Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK

    F. Xavier Donadeu

Authors
  1. Cristina L. Esteves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Xavier Donadeu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cristina L. Esteves .

Editor information

Editors and Affiliations

  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Alexander Birbrair

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Esteves, C.L., Donadeu, F.X. (2018). Pericytes in Veterinary Species: Prospective Isolation, Characterization and Tissue Regeneration Potential. In: Birbrair, A. (eds) Pericyte Biology - Novel Concepts. Advances in Experimental Medicine and Biology, vol 1109. Springer, Cham. https://doi.org/10.1007/978-3-030-02601-1_6

Download citation

Publish with us

Policies and ethics

Search

Navigation