Skip to main content

Fetal Adnexa-Derived Stem Cells Application in Horse Model of Tendon Disease

  • Chapter
  • First Online:
Book cover Stem Cells in Animal Species: From Pre-clinic to Biodiversity

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

  • 603 Accesses

Abstract

The equine superficial digital flexor tendon is a frequently injured structure that is functionally and clinically equivalent to the human Achilles tendon. Both act as critical energy-storage systems during high-speed locomotion and can accumulate exercise- and age-related microdamage that predisposes to rupture during normal activity.

The biology of tendon and its matrix, and the pathological changes occurring in the context of early injury in both horses and people are reviewed. In addition, this review focuses on the current use of stem cells (MSCs), recovered from either bone marrow or adipose tissue to treat strain-induced tendon injury in the horse with particular interest to non-embryonic extra-fetal-derived stem cells that open new perspectives for developmental biology and for regenerative medicine.

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

Access this chapter

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

  • Abrahamsson SO, Gelberman R (1994) Maintenance of the gliding surface of tendon autografts in dogs. Acta Orthop Scand 65:548–552. doi:10.1016/j.jhsa.2007.09.007

    CAS  PubMed  Google Scholar 

  • Abrahamsson SO, Lohmander S (1996) Differential effects of insulin-like growth factor-I on matrix and DNA synthesis in various regions and types of rabbit tendons. J Orthop Res 14:370–376. doi:10.1002/jor.1100140305

    CAS  PubMed  Google Scholar 

  • Abrahamsson SO, Lundborg G, Lohmander LS (1991) Long-term explant culture of rabbit flexor tendon: effects of recombinant human insulin-like growth factor-I and serum on matrix metabolism. J Orthop Res 9:503–515

    CAS  PubMed  Google Scholar 

  • Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822. doi:10.1182/blood-2004-04-1559

    CAS  PubMed  Google Scholar 

  • Alexander RW (2012) Understanding adipose-derived stromal vascular fraction (AD-SVF) cell biology and use on the basis of cellular, chemical, structural and paracrine components: a concise review. J Prolother 4:e855–e869

    Google Scholar 

  • Alves A, Stewart A, Dudhia J (2011) Cell-based therapies for tendon and ligament incurie. Vet Clin North Am Equine Pract 27:315–333. doi:10.1016/j.cveq.2011.06.001

    CAS  PubMed  Google Scholar 

  • Astrom M, Rausing A (1995) Chronic Achilles tendinopathy. A survey of surgical and histopathologic findings. Clin Orthop Relat Res 316:151–164

    PubMed  Google Scholar 

  • Awad HA, Boivin GP, Dressler MR et al (2003) Repair of patellar tendon injuries using a cell-collagen composite. J Orthop Res 21:420–431

    CAS  PubMed  Google Scholar 

  • Barboni B, Russo V, Curini V et al (2012) Achilles tendon regeneration can be improved by amniotic epithelial cell allotransplantation. Cell Transplant 21:2377–2395

    CAS  PubMed  Google Scholar 

  • Berg L, Koch T, Heerkens T et al (2009) Chondrogenic potential of mesenchymal stromal cells derived from equine bone marrow and umbilical cord blood. Vet Comp Orthop Traumatol 22:363–370. doi:10.3415/VCOT-08-10-0107

    CAS  PubMed  Google Scholar 

  • Bi Y, Ehirchiou D, Kilts TM et al (2007) Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med 13:1219–1227

    CAS  PubMed  Google Scholar 

  • Birch HL, Bailey JVB, Bailey AJ et al (1999) Age-related changes to the molecular and cellular components of equine flexor tendons. Equine Vet J 31:391–396

    CAS  PubMed  Google Scholar 

  • Burk J, Brehm W (2011) Stammzellentherapie von Sehnenverletzungen—klinische Ergebnisse von 98 Fällen. Pferdeheilkunde 27:153–161

    Google Scholar 

  • Butler DL, Juncosa-Melvin N, Boivin GP et al (2008) Functional tissue engineering for tendon repair: a multidisciplinary strategy using mesenchymal stem cells, bioscaffolds, and mechanical stimulation. J Orthop Res 26:1–9. doi:10.1002/jor.20456

    PubMed  Google Scholar 

  • Campbell BH, Agarwal C, Wang JH (2004) TGF-beta1, TGFbeta3, and PGE(2) regulate contraction of human patellar tendon fibroblasts. Biomech Model Mechanobiol 2:239–245. doi:10.1007/s10237-004-0041-z

    CAS  PubMed  Google Scholar 

  • Cargnoni A, Gibelli L, Tosini A et al (2009) Transplantation of allogeneic and xenogeneic placenta-derived cells reduces bleomycin-induced lung fibrosis. Cell Transplant 18:405–422. doi:10.3727/096368909788809857

    PubMed  Google Scholar 

  • Cargnoni A, Ressel L, Rossi D et al (2012) Conditioned medium from amniotic mesenchymal tissue cells reduces progression of bleomycin-induced lung fibrosis. Cytotherapy 14:153–161. doi:10.3109/14653249.2011.613930

    CAS  PubMed Central  PubMed  Google Scholar 

  • Carrade DD, Owens SD, Galuppo LD et al (2011) Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses. Cytotherapy 13:419–430. doi:10.3109/14653249.2010.536213

    CAS  PubMed  Google Scholar 

  • Chabannes D, Hill M, Merieau E et al (2007) A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 110:3691–3694. doi:10.1182/blood-2007-02-075481

    CAS  PubMed  Google Scholar 

  • Chan BP, Leong K (2008) Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur Spine J 17(suppl 4):467–479. doi:10.1007/s00586-008-0745-3

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cheung DT, DiCesare P, Benya PD et al (1983) The presence of inter molecular cross-links in type III collagen. J Biol Chem 12:7774–7778

    Google Scholar 

  • Chong AK, Chang J, Go JC (2009) Mesenchymal stem cells and tendon healing. Front Biosci 14:4598–4605

    CAS  Google Scholar 

  • Cohen RE, Hooley CJ, McCrum NG (1974) Mechanism of the viscoelastic deformation of collagenous tissue. Nature 247:59–61

    CAS  PubMed  Google Scholar 

  • Colleoni S, Bottani E, Tessaro I et al (2009) Isolation, growth and differentiation of equine mesenchymal stem cells: effect of donor, source, amount of tissue and supplementation with basic fibroblast growth factor. Vet Res Commun 33:811–821. doi:10.1007/s11259-009-9229-0

    PubMed  Google Scholar 

  • Cook JL, Feller JA, Bonar SF et al (2004) Abnormal tenocyte morphology is more prevalent than collagen disruption in asymptomatic athletes’ patellar tendons. J Orthop Res 22:334–338

    CAS  PubMed  Google Scholar 

  • 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. doi:10.1111/j.1365-2184.2011.00759.x

    CAS  PubMed  Google Scholar 

  • Cremonesi F, Corradetti B, Lange Consiglio A (2011) Fetal adnexa derived stem cells from domestic animal: progress and perspectives. Theriogenology 75:1400–1415. doi:10.1016/j.theriogenology.2010.12.032

    CAS  PubMed  Google Scholar 

  • Crevier-Denoix N, Pourcelot P (1997) Additional research on tendon strains and stresses. Am J Vet Res 58:569–570

    CAS  PubMed  Google Scholar 

  • Crovace A, Lacitignola L, De Siena R, Rossi G, and Francioso E. (2007) Cell therapy for tendon repair in horses: an experimental study. Vet Res Commun 31: supplement 1, 281–283

    Google Scholar 

  • Crovace A, Lacitignola L, Rossi G et al (2010) Histological and immunohistochemical evaluation of autologous cultured bone marrow mesenchymal stem cells and bone marrow mononucleated cells in collagenase-induced tendinitis of equine superficial digital flexor tendon. Vet Med Int 2010:250978. doi:10.4061/2010/250978

    PubMed Central  PubMed  Google Scholar 

  • da Silva Meirelles L, Chagastelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119:2204–2213

    PubMed  Google Scholar 

  • Dahlgren LA (2009) Fat-derived mesenchymal stem cells for equine tendon repair. Regen Med 4: Suppl.2, S14

    Google Scholar 

  • Dahlgren LA, van der Meulen MC, Bertram JE et al (2002) Insulin-like growth factor-I improves cellular and molecular aspects of healing in a collagenase induced model of flexor tendinitis. J Orthop Res 20:910–919

    CAS  PubMed  Google Scholar 

  • de Mos M, Koevoet WJ, Jahr H et al (2007) Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study. BMC Musculoskelet Disord 8:16

    PubMed Central  PubMed  Google Scholar 

  • Del Bue M, Ricco S, Ramoni R et al (2008) Equine adipose-tissue derived mesenchymal stem cells and platelet concentrates: their association in vitro and in vivo. Vet Res Commun 32(suppl 1):S51–S55. doi:10.1007/s11259-008-9093-3

    PubMed  Google Scholar 

  • Dowling BA, Dart AJ, Hodgson DR et al (2000) Superficial digital flexor tendonitis in the horse. Equine Vet J 32:369–378

    CAS  PubMed  Google Scholar 

  • Dunphy JE (1967) The healing of wounds. Can J Surg 10:281–287

    CAS  PubMed  Google Scholar 

  • Durando MM, Zarucco L, Schaer TP et al (2006) Pneumopericardium in a horse secondary to sternal bone marrow aspiration. Equine Vet Educ 18:75–79

    Google Scholar 

  • Dyson SJ (2004) Medical management of superficial digital flexor tendonitis: a comparative study in 219 horses (1992-2000). Equine Vet J 36:415–419

    CAS  PubMed  Google Scholar 

  • Ely ER, Avella CS, Price JS et al (2009) Descriptive epidemiology of fracture, tendon and suspensory ligament injuries in National Hunt racehorses in training. Equine Vet J 41:372–378

    CAS  PubMed  Google Scholar 

  • Emerson C, Morrissey D, Perry M et al (2010) Ultrasonographically detected changes in Achilles tendons and self reported symptoms in elite gymnasts compared with controls—an observational study. Man Ther 15:37–42. doi:10.1016/j.math.2009.05.008

    PubMed  Google Scholar 

  • Engela AU, Baan CC, Dor FJ et al (2012) On the interactions between mesenchymal stem cells and regulatory T cells for immunomodulation in transplantation. Front Immunol 3:126. doi:10.3389/fimmu.2012.00126

    PubMed Central  PubMed  Google Scholar 

  • Eriksen HA, Pajala A, Leppilahti J et al (2002) Increased content of type III collagen at the rupture site of human Achilles tendon. J Orthop Res 20:1352–1357

    CAS  PubMed  Google Scholar 

  • Evangelista M, Soncini M, Parolini O (2008) Placenta-derived stem cells: new hope for cell therapy? Cytotechnology 58:33–42

    Google Scholar 

  • Evans CE, Trail IA (2001) An in vitro comparison of human flexor and extensor tendon cells. J Hand Surg Br 26:307–313

    CAS  PubMed  Google Scholar 

  • Farris DJ, Trewartha G, McGuigan MP (2011) Could intra-tendinous hyperthermia during running explain chronic injury of the human Achilles tendon? J Biomech 44:822–826. doi:10.1016/j.jbiomech.2010.12.015

    PubMed  Google Scholar 

  • Fenwick S, Harral R, Hacney R et al (2002) Endochondral ossification in Achilles and patella tendinopathy. Rheumatology (Oxford) 41:474–476

    CAS  Google Scholar 

  • Fortier LA, Smith RK (2008) Regenerative medicine for tendinous and ligamentous injuries of sport horses. Vet Clin North Am Equine Pract 24:191–201. doi:10.1016/j.cveq.2007.11.002

    PubMed  Google Scholar 

  • Fortier LA, Travis AJ (2011) Stem cells in veterinary medicine. Stem Cell Res Ther 2:9. doi:10.1186/scrt50

    PubMed Central  PubMed  Google Scholar 

  • Fortier LA, Nixon AJ, Williams J et al (1998) Isolation and chondrocytic differentiation of equine bone marrow-derived mesenchymal stem cells. Am J Vet Res 59:1182–1187

    CAS  PubMed  Google Scholar 

  • Fortier LA, Potter HG, Rickey EJ et al (2010) Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am 92:1927–1937. doi:10.2106/JBJS.I.01284

    PubMed  Google Scholar 

  • Garner WL, McDonald JA, Koo M (1989) Identification of the collagen-producing cells in healing flexor tendons. Plast Reconstr Surg 83:875–879

    CAS  PubMed  Google Scholar 

  • Genovese RL, Reef VB, Longo KL et al (1996) Superficial digital flexor tendonitis long term sonographic and clinical study of racehorses. In: Rantanen NW, Hauser ML (eds) Proceedings of the Dubai equine international symposium, Dubai, pp 187–205

    Google Scholar 

  • Gillis C, Meagher DM, Cloninger A et al (1995a) Ultrasonographic cross-sectional area and mean echogenicity of the superficial and deep digital flexor tendons in 50 trained Thoroughbred racehorses. Am J Vet Res 56:1265–1269

    CAS  PubMed  Google Scholar 

  • Gillis C, Sharkey N, Stover S et al (1995b) Effect of maturation and aging on material and ultrasonographic properties of equine superficial digital flexor tendon. Am J Vet Res 56:1345–1350

    CAS  PubMed  Google Scholar 

  • Gillis C, Pool RR, Meagher DM et al (1997) Effect of maturation and aging on the histomorphometric and biochemical characteristics of equine superficial digital flexor tendon. Am J Vet Res 58:425–430

    CAS  PubMed  Google Scholar 

  • Godwin EE, Young NJ, Dudhia J et al (2012) Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. Equine Vet J 44:25–32. doi:10.1111/j.2042-3306.2011.00363.x

    CAS  PubMed  Google Scholar 

  • Goodship AE, Birch HL (1996) The pathophysiology of the flexor tendons in the equine athlete. In: Rantanen NW, Hauser ML (eds) Proceedings of the Dubai equine international symposium, Dubai, pp 83–107

    Google Scholar 

  • Goodship AE, Birch HL, Wilson AM (1994) The pathobiology and repair of tendon and ligament injury. Vet Clin North Am Equine Pract 10:323–348

    CAS  PubMed  Google Scholar 

  • Gu J, Wada Y (1996) Effect of exogenous Decorin on cell morphology and attachment of Decorin-deficient fibroblasts. J Biochem 119:743–748

    CAS  PubMed  Google Scholar 

  • Guest DJ, Smith MR, Allen WR (2008) Monitoring the fate of autologous and allogeneic mesenchymal progenitor cells injected into the superficial digital flexor tendon of horses: preliminary study. Equine Vet J 40:178–181. doi:10.2746/042516408X276942

    CAS  PubMed  Google Scholar 

  • Guest DJ, Smith MR, Allen WR (2010) Equine embryonic stem-like cells and mesenchymal stromal cells have different survival rates and migration patterns following their injection into damaged superficial digital flexor tendon. Equine Vet J 42:636–642. doi:10.1111/j.2042-3306.2010.00112.x

    CAS  PubMed  Google Scholar 

  • Hankemeier S, Keus M, Zeichen J et al (2005) Modulation of proliferation and differentiation of human bone marrow stromal cells by fibroblast growth factor 2: potential implications for tissue engineering of tendons and ligaments. Tissue Eng 11:41–49

    CAS  PubMed  Google Scholar 

  • Hankemeier S, van Griensven M, Ezechieli M et al (2007) Tissue engineering of tendons and ligaments by human bone marrow stromal cells in a liquid fibrin matrix in immunodeficient rats: results of a histologic study. Arch Orthop Trauma Surg 127:815–821

    PubMed  Google Scholar 

  • Heinemeier K, Langberg H, Olesen JL et al (2003) Role of TGF-beta1 in relation to exercise-induced type I collagen synthesis in human tendinous tissue. J Appl Physiol 95:2390–2397

    CAS  PubMed  Google Scholar 

  • Herrero C, Pérez-Simón JA (2010) Immunomodulatory effect of mesenchymal stem cells. Braz J Med Biol Res 43:425–430

    CAS  PubMed  Google Scholar 

  • Hertel D (2001) Enhanced suspensory ligament healing in 100 horses by stem cells and other bone marrow components. Proc Am Assoc Equine Pract 47:319–321

    Google Scholar 

  • Hooley CJ, McCrum NG, Cohen RE (1980) The viscoelastic deformation of tendon. J Biomech 13:521–528

    CAS  PubMed  Google Scholar 

  • Ingraham JM, Hauck RM, Ehrlich HP (2003) Is the tendon embryogenesis process resurrected during tendon healing? Plast Reconstr Surg 112:844–854

    PubMed  Google Scholar 

  • Jarvinen M, Jozsa L, Kannus P et al (1997) Histopathological findings in chronic tendon disorders. Scand J Med Sci Sports 7:86–95

    CAS  PubMed  Google Scholar 

  • Jezierska-Woźniak K, Nosarzewska D, Tutas A et al (2010) Use of adipose tissue as a source of mesenchymal stem cells. Postepy Hig Med Dosw (Online) 64:326–332

    Google Scholar 

  • Jones AJ (1993) Normal and diseased equine digital flexor tendon: blood flow, biochemical and serological studies. PhD Thesis, University of London, London

    Google Scholar 

  • Jones G, Corps A, Pennington C et al (2006) Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human Achilles tendon. Arthritis Rheum 54:832–842. doi:10.1002/art.21672

    CAS  PubMed  Google Scholar 

  • Juncosa-Melvin N, Matlin KS, Holdcraft RW et al (2007) Mechanical stimulation increases collagen type I and collagen type III gene expression of stem cell-collagen sponge constructs for patellar tendon repair. Tissue Eng 13:1219–1226

    CAS  PubMed  Google Scholar 

  • Kader D, Saxena A, Movin T et al (2002) Achilles tendinopathy: some aspects of basic science and clinical management. Br J Sports Med 36:239–249

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kajikawa Y, Morihara T, Watanabe N et al (2007) GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing. J Cell Physiol 210:684–691

    CAS  PubMed  Google Scholar 

  • Kannus P, Jozsa L (1991) Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am 73:1507–1525

    CAS  PubMed  Google Scholar 

  • Kasashima Y, Kuwano A, Katayama Y et al (2002) Magnetic resonance imaging application to live horse for diagnosis of tendinitis. J Vet Med Sci 64:577–582

    PubMed  Google Scholar 

  • Kasashima Y, Takahashi T, Smith RK et al (2004) Prevalence of superficial digital flexor tendonitis and suspensory desmitis in Japanese Thoroughbred flat racehorses in 1999. Equine Vet J 36:346–350

    CAS  PubMed  Google Scholar 

  • Kashiwagi K, Mochizuki Y, Yasunaga Y et al (2004) Effects of transforming growth factor-beta 1 on the early stages of healing of the Achilles tendon in a rat model. Scand J Plast Reconstr Surg Hand Surg 38:193–197

    PubMed  Google Scholar 

  • Kastelic J, Baer E (1980) Deformation in tendon collagen. Symp Soc Exp Biol 34:397–435

    CAS  PubMed  Google Scholar 

  • Kisiday JD, Kopesky PW, Evans CH et al (2008) Evaluation of adult equine bone marrow- and adipose-derived progenitor cell chondrogenesis in hydrogel cultures. J Orthop Res 26:322–331

    CAS  PubMed  Google Scholar 

  • Klein MB, Yalamanchi N, Pham H et al (2002) Flexor tendon healing in vitro: effects of TGF-beta on tendon cell collagen production. J Hand Surg Am 27A:615–620

    Google Scholar 

  • Knobloch K, Yoon U, Vogt PM (2008) Acute and overuse injuries correlated to hours of training in master running athletes. Foot Ankle Int 29:671–676

    PubMed  Google Scholar 

  • Kraus-Hansen AE, Fackelman GE, Becker C et al (1992) Preliminary studies on the vascular anatomy of the equine superficial digital flexor tendon. Equine Vet J 24:46–51

    CAS  PubMed  Google Scholar 

  • Kryger GS, Chong AK, Costa M et al (2007) A comparison of tenocytes and mesenchymal stem cells for use in flexor tendon tissue engineering. J Hand Surg Am 32:597–605

    PubMed  Google Scholar 

  • Kurtz CA, Loebig TG, Anderson DD et al (1999) Insulin-like growth factor I accelerates functional recovery from Achilles tendon injury in a rat model. Am J Sports Med 27:363–369

    CAS  PubMed  Google Scholar 

  • Lacitignola L, Crovace A, Rossi G, Francioso E (2008) Cell therapy for tendinitis, experimental and clinical report.Vet Res Commun:S33–S38.

    Google Scholar 

  • Lange-Consiglio A, Corradetti B, Bizzaro D et al (2012) Characterization and potential applications of progenitor-like cells isolated from horse amniotic membrane. J Tissue Eng Regen Med 6:622–635. doi:10.1002/term.465

    CAS  PubMed  Google Scholar 

  • Lange-Consiglio A, Corradetti B, Meucci A et al (2013a) Characteristics of equine mesenchymal stem cells derived from amnion and bone marrow: in vitro proliferative and multilineage potential assessment. Equine Vet J. 45:737–744. doi:10.1111/evj.12052

    CAS  PubMed  Google Scholar 

  • Lange-Consiglio A, Tassan S, Corradetti B et al (2013b) Investigating the potential of equine mesenchymal stem cells derived from amnion and bone marrow in equine tendon diseases treatment in vivo. Cytotherapy 15:1011–1020. doi: 10.1016/J.JCYT.2013.03.002

  • Lange-Consiglio A, Rossi D, Tassan S et al (2013c) Conditioned medium from horse amniotic membrane-derived multipotent progenitor cells: immunomodulatory activity in vitro and first clinical application in tendon and ligament injuries in vivo. Stem Cell Dev 22:3015–3024. doi:10.1089/scd.2013.0214

  • Leadbetter WB (1992) Cell-matrix response in tendon injury. Clin Sports Med 11:533–578

    CAS  PubMed  Google Scholar 

  • Leppänen M, Miettinen S, Mäkinen S et al (2009) Management of equine tendon & ligament injuries with expanded autologous adipose-derived mesenchymal stem cells: a clinical study. Regen Med 4(suppl 2):21

    Google Scholar 

  • Lindsay WK, Birch JR (1964) The fibroblast in flexor tendon healing. Plast Reconstr Surg 34:223–232

    CAS  PubMed  Google Scholar 

  • Liu SH, Yang RS, al-Shaikh R, Lane JM (1995) Collagen in tendon, ligament, and bone healing. A current review. Clin Orthop Relat Res 318:265–278

    PubMed  Google Scholar 

  • Liu W, Chen B, Deng D et al (2006) Repair of tendon defect with dermal fibroblast engineered tendon in a porcine model. Tissue Eng 12:775–788

    PubMed  Google Scholar 

  • Lovati AB, Corradetti B, Lange Consiglio A et al (2011) Characterization and differentiation of equine tendon-derived progenitor cells. J Biol Regul Homeost Agents 25(2 suppl):S75–S84

    CAS  PubMed  Google Scholar 

  • Magatti M, De Munari S, Vertua E et al (2008) Human amnion mesenchyme harbors cells with allogeneic T-cell suppression and stimulation capabilities. Stem Cells 26:182–192

    CAS  PubMed  Google Scholar 

  • Malvankar S, Khan WS (2011) Evolution of the Achilles tendon: the athlete’s Achilles heel? Foot (Edinburgh) 21:193–197

    CAS  Google Scholar 

  • Martinello T, Bronzini I, Maccatrozzo L et al (2011) Canine adipose-derived-mesenchymal stem cells do not lose stem features after a long-term cryopreservation. Res Vet Sci 91:18–24. doi:10.1016/j.foot.2011.08.004

    CAS  PubMed  Google Scholar 

  • McIlwraith CW (1987) Diseases of joints, tendons, ligaments, and related structures. In: Stashak TS (ed) Adams’ lameness in horses. Lea & Febiger, Philadelphia, pp 339–485

    Google Scholar 

  • Meirelles LS, Fontes AM, Covas DT et al (2009) Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20:419–427

    CAS  Google Scholar 

  • Millar NL, Reilly JH, Kerr SC et al (2012) Hypoxia: a critical regulator of early human tendinopathy. Ann Rheum Dis 71:302–310. doi:10.1136/ard.2011.154229

    CAS  PubMed  Google Scholar 

  • Minetti AE, ArdigO LP, Reinach E et al (1999) The relationship between mechanical work and energy expenditure of locomotion in horses. J Exp Biol 202:2329–2338

    CAS  PubMed  Google Scholar 

  • Murphy JM, Fink DJ, Hunziker EB et al (2003) Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 48:3464–3474

    PubMed  Google Scholar 

  • Muttini A, Valbonetti L, Abate M et al (2013) Ovine amniotic epithelial cells: in vitro characterization and transplantation into equine superficial digital flexor tendon spontaneous defects. Res Vet Sci 94:158–169. doi:10.1016/j.rvsc.2012.07.028

    CAS  PubMed  Google Scholar 

  • Myers B, Wolf M (1974) Vascularization of the healing wound. Am Surg 40:716–722

    CAS  PubMed  Google Scholar 

  • Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499–3506

    CAS  PubMed  Google Scholar 

  • Nixon AJ, Dahlgren LA, Haupt JL et al (2008) Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis. Am J Vet Res 69:928–937. doi:10.2460/ajvr.69.7.928

    CAS  PubMed  Google Scholar 

  • O’Meara BO, Bladon B, Parkin TDH et al (2010) An investigation of the relationship between race performance and superficial digital flexor tendonitis in the thoroughbred racehorse. Equine Vet J 42:322–326. doi:10.1111/j.2042-3306.2009.00021.x

    PubMed  Google Scholar 

  • Pacini S, Spinabella S, Trombi L et al (2007). Suspension of bone marrow-derived undifferentiated mesenchymal stromal cells for repair of superficial digital flexor tendon in race horses. Tissue Eng 13:2949–2955

    Google Scholar 

  • Paris DB, Stout TA (2010) Equine embryos and embryonic stem cells: defining reliable markers of pluripotency. Theriogenology 74:516–524. doi:10.1016/j.theriogenology.2009.11.020

    CAS  PubMed  Google Scholar 

  • Patterson-Kane JC, Firth EC, Goodship AE et al (1997a) Age related differences in collagen crimp patterns in the superficial digital flexor tendon core region of untrained horses. Aust Vet J 75:39–44

    CAS  PubMed  Google Scholar 

  • Patterson-Kane JC, Parry DA, Birch HL et al (1997b) An age-related study of morphology and cross-link composition of collagen fibrils in the digital flexor tendons of young Thoroughbred horses. Connect Tissue Res 36:253–260

    CAS  PubMed  Google Scholar 

  • Patterson-Kane JC, Wilson AM, Firth EC et al (1997c) Comparison of collagen fibril populations in the superficial flexor tendon of exercised and nonexercised Thoroughbreds. Equine Vet J 29:121–125

    CAS  PubMed  Google Scholar 

  • Patterson-Kane JC, Becker DL, Rich T (2012) Spontaneously arising disease: review article. The pathogenesis of tendon microdamage in athletes: the horse as a natural model for basic cellular research. J Comp Pathol 147:227–247. doi:10.1016/j.jcpa.2012.05.010

    CAS  PubMed  Google Scholar 

  • Perez-Castro AV, Vogel KG (1999) In situ expression of collagen and proteoglycan genes during development of fibrocartilage in bovine deep flexor tendon. J Orthop Res 17:139–148

    CAS  PubMed  Google Scholar 

  • Perkins NR, Reid SW, Morris RS (2005) Risk factors for injury to the superficial digital flexor tendon and suspensory apparatus in Thoroughbred racehorses in New Zealand. N Z Vet J 53:184–192

    CAS  PubMed  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    CAS  PubMed  Google Scholar 

  • Pool RR (1996) Pathologic changes in tendonitis of athletic horses. In: Rantanen NW, Hauser ML (eds) Proceedings of the Dubai equine international symposium, Dubai, pp 109–117

    Google Scholar 

  • Pruzansky ME (1987) A primate model for the evaluation of tendon adhesions. J Surg Res 42:273–276

    CAS  PubMed  Google Scholar 

  • Rees JD, Wilson AM, Wolman RL (2006) Current concepts in the management of tendon disorders. Rheumatology 45:508–521

    CAS  PubMed  Google Scholar 

  • Ren G, Zhang L, Zhao X et al (2008) Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2:141–150. doi:10.1016/j.stem.2007.11.014

    CAS  PubMed  Google Scholar 

  • Richardson LE, Dudhia J, Clegg PD et al (2007) Stem cells in veterinary medicine-attempts at regenerating equine tendon after injury. Trends Biotechnol 25:409–416, PubMed PMID: 17692415.eng

    CAS  PubMed  Google Scholar 

  • Riemersa DJ, Schamhardt HC (1982) The cryo-jaw, a clamp designed for in vitro rheology studies of horse digital flexor tendons. J Biomech 15:619–620

    CAS  PubMed  Google Scholar 

  • Riley GP (2005) Gene expression and matrix turnover in overused and damaged tendons. Scand J Med Sci Sports 15:241–251

    CAS  PubMed  Google Scholar 

  • Riley GP, Harrall RL, Constant CR et al (1994a) Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis. Ann Rheum Dis 53:359–366

    CAS  PubMed Central  PubMed  Google Scholar 

  • Riley GP, Harrall RL, Constant CR et al (1994b) Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis. Ann Rheum Dis 53:367–376

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rolf CG, Fu BSC, Pau A et al (2001) Increased cell proliferation and associated expression of PDGFRb causing hypercellularity in patellar tendinosis. Rheumatology 40:256–261

    CAS  PubMed  Google Scholar 

  • Roshan J, Kesturu G, Balian G et al (2008) Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. Hand Surg 33A:102–112

    Google Scholar 

  • Rossi D, Pianta S, Magatti M et al (2012) Characterization of the conditioned medium from amniotic membrane cells: prostaglandins as key effectors of its immunomodulatory activity. PLoS One 7:e46956. doi:10.1371/journal.pone.0046956

    CAS  PubMed Central  PubMed  Google Scholar 

  • Salingcarnboriboon R, Yoshitake H, Tsuji K et al (2003) Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property. Exp Cell Res 287:289–300

    CAS  PubMed  Google Scholar 

  • Saxena A, Ewen B, Maffulli N (2011) Rehabilitation of the operated Achilles tendon: parameters for predicting a return to activity. J Foot Ankle Surg 50:37–40. doi:10.1053/j.jfas.2010.10.008

    PubMed  Google Scholar 

  • Schnabel LV, Lynch ME, van der Meulen MC et al (2009) Mesenchymal stem cells and insulin-like growth factor-I gene-enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons. J Orthop Res 27:1392–1398. doi:10.1002/jor.20887

    CAS  PubMed  Google Scholar 

  • Selmani Z, Naji A, Zidi I et al (2008) Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells 26:212–222

    CAS  PubMed  Google Scholar 

  • Seo BM, Miura M, Gronthos S et al (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364:149–155

    CAS  PubMed  Google Scholar 

  • Sharma P, Maffulli N (2005a) Basic biology of tendon injury and healing. Surgeon 3:309–316

    CAS  PubMed  Google Scholar 

  • Sharma P, Maffulli N (2005b) Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg 87:187–202

    PubMed  Google Scholar 

  • Silver IA, Brown PM, Goodship AE (1983) A clinical and experimental study of tendon injury, healing and treatment in the horse. Equine vet J Suppl 1:1–43

    PubMed  Google Scholar 

  • Smith RK (2008) Mesenchymal stem cell therapy for equine tendinopathy. Disabil Rehabil 30:1752–1758. doi:10.1080/09638280701788241

    PubMed  Google Scholar 

  • Smith RKW, Webbon PM (1996) The physiology of normal tendon and ligament. In: Rantanen NW, Hauser ML (eds) Proceedings of the Dubai equine international symposium, Dubai, pp 55–81

    Google Scholar 

  • Smith RKW, Jones R, Webbon PM (1994) The cross-sectional areas of normal equine digital flexor tendons determined ultrasonographically. Equine Vet J 26:460–465

    CAS  PubMed  Google Scholar 

  • Smith RK, Zunino L, Webbon PM et al (1997) The distribution of cartilage oligomeric matrix protein (COMP) in tendon and its variation with tendon site, age and load. Matrix Biol 16:255–271

    CAS  PubMed  Google Scholar 

  • Smith RK, Korda M, Blunn GW et al (2003) Isolation and implantation of autologous equine mesenchymal stem cells from bone marrow into the superficial digital flexor tendon as a potential novel treatment. Equine Vet J 35:99–102

    CAS  PubMed  Google Scholar 

  • Smith AM, Forder JA, Annapureddy SR et al (2005) The porcine forelimb as a model for human flexor tendon surgery. J Hand Surg Br 30B:307–309

    Google Scholar 

  • Smith R, Young N, Dudhia J et al (2009) Effectiveness of bone-marrow-derived mesenchymal progenitor cells for naturally occurring tendinopathy in the horse. Regen Med 4(suppl 2):25–26

    Google Scholar 

  • Tang YL, Zhao Q, Zhang YC et al (2004) Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul Pept 117:3–10

    CAS  PubMed  Google Scholar 

  • Thomopoulos S, Harwood FL, Silva MJ et al (2005) Effect of several growth factors on canine flexor tendon fibroblast proliferation and collagen synthesis in vitro. J Hand Surg Am 30A:441–447

    Google Scholar 

  • Thorpe CT, Clegg PD, Birch HL (2010) A review of tendon injury: why is the equine superficial digital flexor tendon most at risk? Equine Vet J 42:174–180. doi:10.2746/042516409X480395

    CAS  PubMed  Google Scholar 

  • Timmers L, Lim SK, Arslan F et al (2007) Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res 1:129–137. doi:10.1016/j.scr.2008.02.002

    CAS  PubMed  Google Scholar 

  • Toupadakis CA, Wong A, Genetos DC et al (2010) Comparison of the osteogenic potential of equine mesenchymal stem cells from bone marrow, adipose tissue, umbilical cord blood, and umbilical cord tissue. Am J Vet Res 71:1237–1245

    PubMed  Google Scholar 

  • Tsuzaki M, Brigman BE, Yamamoto J et al (2000) Insulin-like growth factor-I is expressed by avian flexor tendon cells. J Orthop Res 18:546–556

    CAS  PubMed  Google Scholar 

  • van Poll D, Parekkadan B, Cho CH et al (2008) Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo. Hepatology 47:1634–1643. doi:10.1002/hep.22236

    PubMed  Google Scholar 

  • Vidal MA, Lopez MJ (2011) Adipogenic differentiation of adult equine mesenchymal stromal cells. Methods Mol Biol 702:61–75. doi:10.1007/978-1-61737-960-4_6

    CAS  PubMed  Google Scholar 

  • Vidal MA, Kilroy GE, Johnson JR et al (2006) Cell growth characteristics and differentiation frequency of adherent equine bone marrow-derived mesenchymal stromal cells: adipogenic and osteogenic capacity. Vet Surg 35:601–610

    PubMed  Google Scholar 

  • Vidal MA, Kilroy GE, Lopez MJ et al (2007) Characterization of equine adipose tissue-derived stromal cells: adipogenic and osteogenic capacity and comparison with bone marrow-derived mesenchymal stromal cells. Vet Surg 36:613–622

    PubMed  Google Scholar 

  • Vidal MA, Robinson SO, Lopez MJ et al (2008) Comparison of chondrogenic potential in equine mesenchymal stromal cells derived from adipose tissue and bone marrow. Vet Surg 37:713–724. doi:10.1111/j.1532-950X.2008.00462.x

    PubMed Central  PubMed  Google Scholar 

  • Vidal MA, Walker NJ, Napoli E et al (2012) Evaluation of senescence in mesenchymal stem cells isolated from equine bone marrow, adipose tissue, and umbilical cord tissue. Stem Cells Dev 21:273–283. doi:10.2460/ajvr.73.9.1435

    PubMed  Google Scholar 

  • Wagner W, Wein F, Seckinger A et al (2005) Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 33:1402–1416

    CAS  PubMed  Google Scholar 

  • Wang XT, Liu PY, Tang JB (2004) Tendon healing in vitro: genetic modification of tenocytes with exogenous PDGF gene and promotion of collagen gene expression. J Hand Surg Am 29A:884–890

    Google Scholar 

  • Watkins JP, Auer JA, Gay S, Morgan SJ (1985) Healing of surgically created defects in the equine superficial digital flexor tendon: Collagen-type transformation and tissue morphologic reorganisation. Am J Vet Res 46:2091–2096

    Google Scholar 

  • Watts AE, Yeager AE, Kopyov OV et al (2011) Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model. Stem Cell Res Ther 2:4. doi:10.1186/scrt45

    PubMed Central  PubMed  Google Scholar 

  • Williams IF, Heaton A, McCullagh KG (1980) Cell morphology and collagen types in equine tendon scar. Res Vet Sci 28:302–310

    CAS  PubMed  Google Scholar 

  • Wilmink J, Wilson AM, Goodship AE (1992) Functional significance of morphology and micromechanics of collagen fibres in relation to partial rupture of the superficial digital flexor tendon in racehorses. Res Vet Sci 53:354–359

    CAS  PubMed  Google Scholar 

  • Wilson AM, Goodship AE (1994) Exercise-induced hyperthermia as a possible mechanism for tendon degeneration. J Biomech 27:899–905

    CAS  PubMed  Google Scholar 

  • Wilson AM, McGuigan MP, Su A et al (2001) Horses damp the spring in their step. Nature 414:895–899

    CAS  PubMed  Google Scholar 

  • Wolbank S, Peterbauer A, Fahrner M et al (2007) Dose-dependent immunomodulatory effect of human stem cells from amniotic membrane: a comparison with human mesenchymal stem cells from adipose tissue. Tissue Eng 13:1173–1183

    CAS  PubMed  Google Scholar 

  • Yagi H, Soto-Gutierrez A, Parekkadan B et al (2010) Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant 19:667–679. doi:10.3727/096368910X508753

    PubMed Central  PubMed  Google Scholar 

  • Yoshimura H, Muneta T, Nimura A et al (2007) Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res 327:449–462

    CAS  PubMed  Google Scholar 

  • Zafar MS, Mahmood A, Maffulli N (2009) Basic science and clinical aspects of Achilles tendinopathy. Sports Med Arthrosc Rev 17:190–197. doi:10.1097/JSA.0b013e3181b37eb7

    Google Scholar 

Download references

Acknowledgments

The Authors thank Dr S. Tassan for providing ultrasound image of tendon core lesion.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anna Lange-Consiglio .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Lange-Consiglio, A., Cremonesi, F. (2014). Fetal Adnexa-Derived Stem Cells Application in Horse Model of Tendon Disease. In: Brevini, T. (eds) Stem Cells in Animal Species: From Pre-clinic to Biodiversity. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-03572-7_4

Download citation

Publish with us

Policies and ethics