Analyze Diet
Tissue engineering2007; 13(12); 2949-2955; doi: 10.1089/ten.2007.0108

Suspension of bone marrow-derived undifferentiated mesenchymal stromal cells for repair of superficial digital flexor tendon in race horses.

Abstract: It has been proven that mesenchymal stromal cells (MSCs) can differentiate into tenocytes. Attempts to repair tendon lesions have been performed, mainly using scaffold carriers in experimental settings. In this article, we describe the clinical use of undifferentiated MSCs in racehorses. Significant clinical recovery was achieved in 9 of 11 horses evaluated using ultrasound analysis and their ability to return to racing. Our results show that the suspension of a small number of undifferentiated MSCs may be sufficient to repair damaged tendons without the use of scaffold support. Ultrasound scanning showed that fibers were correctly oriented. By using undifferentiated cells, no ectopic bone deposition occurred. A sufficient number of cells was recovered for therapeutic purposes in all but 1 case. We suggest that the use of autologous MSCs is a safe therapeutic method for treating incompletely (i.e., not full-thickness) damaged tendons.
Publication Date: 2007-10-09 PubMed ID: 17919069DOI: 10.1089/ten.2007.0108Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study shows that the injection of mesenchymal stromal cells (MSCs), extracted directly from an animal’s bone marrow, can fix partially damaged tendons in racehorses without requiring scaffolds to support the cells.

Overview of the Research

  • The research explored the possibility of repairing tendon lesions in racehorses by injecting them with undifferentiated MSCs – a type of cell that has the ability to grow (differentiate) into tenocytes, which are the cells that make up tendons.
  • The study was driven by previous experimental attempts which used scaffold carriers to support and position the MSCs in the area of the lesion. In contrast, this study investigated the use of MSCs without the additional support of a scaffold.

Methodology and Findings

  • For the study, the researchers isolated MSCs from the bone marrow of the horses and then injected those undifferentiated cells into the damaged sections of the tendons.
  • The effectiveness of this treatment was evaluated using ultrasound images of the healed tendons, whether the horses could return to racing, and whether the fibres were properly oriented in the healed tendons.
  • Significant clinical recovery was observed in 9 out of 11 horse cases. This suggests that only a small number of undifferentiated MSCs is required to repair the damaged tendons, even without any scaffold support.
  • Importantly, because only undifferentiated cells were used, there were no instances of misplaced bone cell development (referred as ectopic bone deposition) in the tendons, which could typically happen when differentiated cells are used.

Conclusions and Recommendations

  • The research concluded that using horse’s own (autologous) MSCs is a safe and effective therapeutic method for treating partially (not full-thickness) damaged tendons.
  • Adequate numbers of these cells could be harvested for transplant in all but one case, showing that the technique could be used widely in treating tendon injuries in horses.

Cite This Article

APA
Pacini S, Spinabella S, Trombi L, Fazzi R, Galimberti S, Dini F, Carlucci F, Petrini M. (2007). Suspension of bone marrow-derived undifferentiated mesenchymal stromal cells for repair of superficial digital flexor tendon in race horses. Tissue Eng, 13(12), 2949-2955. https://doi.org/10.1089/ten.2007.0108

Publication

ISSN: 1076-3279
NlmUniqueID: 9505538
Country: United States
Language: English
Volume: 13
Issue: 12
Pages: 2949-2955

Researcher Affiliations

Pacini, Simone
  • Center for the Clinical Use of Stem Cells and Hematology Division, Department of Oncology, Transplants, and Advances in Medicine, University of Pisa, Pisa, Italy.
Spinabella, Silvia
    Trombi, Luisa
      Fazzi, Rita
        Galimberti, Sara
          Dini, Francesca
            Carlucci, Fabio
              Petrini, Mario

                MeSH Terms

                • Animals
                • Bone Marrow Transplantation / methods
                • Bone Marrow Transplantation / veterinary
                • Cell Differentiation
                • Chondrocytes / pathology
                • Female
                • Horses / anatomy & histology
                • Horses / injuries
                • Horses / surgery
                • Humans
                • Male
                • Mesenchymal Stem Cell Transplantation / methods
                • Mesenchymal Stem Cell Transplantation / veterinary
                • Tendon Injuries / pathology
                • Tendon Injuries / surgery
                • Tendon Injuries / veterinary
                • Treatment Outcome

                Citations

                This article has been cited 57 times.
                1. El-Husseiny HM, Mady EA, Helal MAY, Tanaka R. The Pivotal Role of Stem Cells in Veterinary Regenerative Medicine and Tissue Engineering.. Vet Sci 2022 Nov 21;9(11).
                  doi: 10.3390/vetsci9110648pubmed: 36423096google scholar: lookup
                2. Bowers K, Amelse L, Bow A, Newby S, MacDonald A, Sun X, Anderson D, Dhar M. Mesenchymal Stem Cell Use in Acute Tendon Injury: In Vitro Tenogenic Potential vs. In Vivo Dose Response.. Bioengineering (Basel) 2022 Aug 22;9(8).
                  doi: 10.3390/bioengineering9080407pubmed: 36004932google scholar: lookup
                3. Voga M, Majdic G. Articular Cartilage Regeneration in Veterinary Medicine.. Adv Exp Med Biol 2022;1401:23-55.
                  doi: 10.1007/5584_2022_717pubmed: 35733035google scholar: lookup
                4. Hagen A, Holland H, Brandt VP, Doll CU, Häußler TC, Melzer M, Moellerberndt J, Lehmann H, Burk J. Platelet Lysate for Mesenchymal Stromal Cell Culture in the Canine and Equine Species: Analogous but Not the Same.. Animals (Basel) 2022 Jan 13;12(2).
                  doi: 10.3390/ani12020189pubmed: 35049811google scholar: lookup
                5. Melzer M, Schubert S, Müller SF, Geyer J, Hagen A, Niebert S, Burk J. Rho/ROCK Inhibition Promotes TGF-β3-Induced Tenogenic Differentiation in Mesenchymal Stromal Cells.. Stem Cells Int 2021;2021:8284690.
                  doi: 10.1155/2021/8284690pubmed: 34659420google scholar: lookup
                6. Prządka P, Buczak K, Frejlich E, Gąsior L, Suliga K, Kiełbowicz Z. The Role of Mesenchymal Stem Cells (MSCs) in Veterinary Medicine and Their Use in Musculoskeletal Disorders.. Biomolecules 2021 Aug 2;11(8).
                  doi: 10.3390/biom11081141pubmed: 34439807google scholar: lookup
                7. Barachini S, Montali M, Panvini FM, Carnicelli V, Gatti GL, Piolanti N, Bonicoli E, Scaglione M, Buda G, Parchi PD. Mesangiogenic Progenitor Cells Are Tissue Specific and Cannot Be Isolated From Adipose Tissue or Umbilical Cord Blood.. Front Cell Dev Biol 2021;9:669381.
                  doi: 10.3389/fcell.2021.669381pubmed: 34291045google scholar: lookup
                8. Meeremans M, Van de Walle GR, Van Vlierberghe S, De Schauwer C. The Lack of a Representative Tendinopathy Model Hampers Fundamental Mesenchymal Stem Cell Research.. Front Cell Dev Biol 2021;9:651164.
                  doi: 10.3389/fcell.2021.651164pubmed: 34012963google scholar: lookup
                9. Hagen A, Lehmann H, Aurich S, Bauer N, Melzer M, Moellerberndt J, Patané V, Schnabel CL, Burk J. Scalable Production of Equine Platelet Lysate for Multipotent Mesenchymal Stromal Cell Culture.. Front Bioeng Biotechnol 2020;8:613621.
                  doi: 10.3389/fbioe.2020.613621pubmed: 33553119google scholar: lookup
                10. Ribitsch I, Baptista PM, Lange-Consiglio A, Melotti L, Patruno M, Jenner F, Schnabl-Feichter E, Dutton LC, Connolly DJ, van Steenbeek FG, Dudhia J, Penning LC. Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do.. Front Bioeng Biotechnol 2020;8:972.
                  doi: 10.3389/fbioe.2020.00972pubmed: 32903631google scholar: lookup
                11. Voga M, Adamic N, Vengust M, Majdic G. Stem Cells in Veterinary Medicine-Current State and Treatment Options.. Front Vet Sci 2020;7:278.
                  doi: 10.3389/fvets.2020.00278pubmed: 32656249google scholar: lookup
                12. Walter SG, Randau TM, Hilgers C, Haddouti EM, Masson W, Gravius S, Burger C, Wirtz DC, Schildberg FA. Molecular and Functional Phenotypes of Human Bone Marrow-Derived Mesenchymal Stromal Cells Depend on Harvesting Techniques.. Int J Mol Sci 2020 Jun 19;21(12).
                  doi: 10.3390/ijms21124382pubmed: 32575596google scholar: lookup
                13. Mocchi M, Dotti S, Bue MD, Villa R, Bari E, Perteghella S, Torre ML, Grolli S. Veterinary Regenerative Medicine for Musculoskeletal Disorders: Can Mesenchymal Stem/Stromal Cells and Their Secretome Be the New Frontier?. Cells 2020 Jun 11;9(6).
                  doi: 10.3390/cells9061453pubmed: 32545382google scholar: lookup
                14. Al Naem M, Bourebaba L, Kucharczyk K, Röcken M, Marycz K. Therapeutic mesenchymal stromal stem cells: Isolation, characterization and role in equine regenerative medicine and metabolic disorders.. Stem Cell Rev Rep 2020 Apr;16(2):301-322.
                  doi: 10.1007/s12015-019-09932-0pubmed: 31797146google scholar: lookup
                15. Chung MJ, Park S, Son JY, Lee JY, Yun HH, Lee EJ, Lee EM, Cho GJ, Lee S, Park HS, Jeong KS. Differentiation of equine induced pluripotent stem cells into mesenchymal lineage for therapeutic use.. Cell Cycle 2019 Nov;18(21):2954-2971.
                  doi: 10.1080/15384101.2019.1664224pubmed: 31505996google scholar: lookup
                16. Zahedi M, Parham A, Dehghani H, Kazemi Mehrjerdi H. Equine bone marrow-derived mesenchymal stem cells: optimization of cell density in primary culture.. Stem Cell Investig 2018;5:31.
                  doi: 10.21037/sci.2018.09.01pubmed: 30498742google scholar: lookup
                17. de Aro AA, Carneiro GD, Teodoro LFR, da Veiga FC, Ferrucci DL, Simões GF, Simões PW, Alvares LE, de Oliveira ALR, Vicente CP, Gomes CP, Pesquero JB, Esquisatto MAM, de Campos Vidal B, Pimentel ER. Injured Achilles Tendons Treated with Adipose-Derived Stem Cells Transplantation and GDF-5.. Cells 2018 Aug 31;7(9).
                  doi: 10.3390/cells7090127pubmed: 30200326google scholar: lookup
                18. Brandt L, Schubert S, Scheibe P, Brehm W, Franzen J, Gross C, Burk J. Tenogenic Properties of Mesenchymal Progenitor Cells Are Compromised in an Inflammatory Environment.. Int J Mol Sci 2018 Aug 28;19(9).
                  doi: 10.3390/ijms19092549pubmed: 30154348google scholar: lookup
                19. Barboni B, Russo V, Berardinelli P, Mauro A, Valbonetti L, Sanyal H, Canciello A, Greco L, Muttini A, Gatta V, Stuppia L, Mattioli M. Placental Stem Cells from Domestic Animals: Translational Potential and Clinical Relevance.. Cell Transplant 2018 Jan;27(1):93-116.
                  doi: 10.1177/0963689717724797pubmed: 29562773google scholar: lookup
                20. Watts AE, Millar NL, Platt J, Kitson SM, Akbar M, Rech R, Griffin J, Pool R, Hughes T, McInnes IB, Gilchrist DS. MicroRNA29a Treatment Improves Early Tendon Injury.. Mol Ther 2017 Oct 4;25(10):2415-2426.
                  doi: 10.1016/j.ymthe.2017.07.015pubmed: 28822690google scholar: lookup
                21. Geburek F, Roggel F, van Schie HTM, Beineke A, Estrada R, Weber K, Hellige M, Rohn K, Jagodzinski M, Welke B, Hurschler C, Conrad S, Skutella T, van de Lest C, van Weeren R, Stadler PM. Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells: a controlled experimental trial.. Stem Cell Res Ther 2017 Jun 5;8(1):129.
                  doi: 10.1186/s13287-017-0564-8pubmed: 28583184google scholar: lookup
                22. Sherman AB, Gilger BC, Berglund AK, Schnabel LV. Effect of bone marrow-derived mesenchymal stem cells and stem cell supernatant on equine corneal wound healing in vitro.. Stem Cell Res Ther 2017 May 25;8(1):120.
                  doi: 10.1186/s13287-017-0577-3pubmed: 28545510google scholar: lookup
                23. Esteves CL, Sheldrake TA, Dawson L, Menghini T, Rink BE, Amilon K, Khan N, Péault B, Donadeu FX. Equine Mesenchymal Stromal Cells Retain a Pericyte-Like Phenotype.. Stem Cells Dev 2017 Jul 1;26(13):964-972.
                  doi: 10.1089/scd.2017.0017pubmed: 28376684google scholar: lookup
                24. Lang HM, Schnabel LV, Cassano JM, Fortier LA. Effect of needle diameter on the viability of equine bone marrow derived mesenchymal stem cells.. Vet Surg 2017 Jul;46(5):731-737.
                  doi: 10.1111/vsu.12639pubmed: 28328147google scholar: lookup
                25. Linderman SW, Gelberman RH, Thomopoulos S, Shen H. Cell and Biologic-Based Treatment of Flexor Tendon Injuries.. Oper Tech Orthop 2016 Sep;26(3):206-215.
                  doi: 10.1053/j.oto.2016.06.011pubmed: 28042226google scholar: lookup
                26. Berglund AK, Schnabel LV. Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies.. Equine Vet J 2017 Jul;49(4):539-544.
                  doi: 10.1111/evj.12647pubmed: 27862236google scholar: lookup
                27. Montali M, Barachini S, Panvini FM, Carnicelli V, Fulceri F, Petrini I, Pacini S. Growth Factor Content in Human Sera Affects the Isolation of Mesangiogenic Progenitor Cells (MPCs) from Human Bone Marrow.. Front Cell Dev Biol 2016;4:114.
                  doi: 10.3389/fcell.2016.00114pubmed: 27800477google scholar: lookup
                28. Scharf A, Holmes SP, Thoresen M, Mumaw J, Stumpf A, Peroni J. MRI-Based Assessment of Intralesional Delivery of Bone Marrow-Derived Mesenchymal Stem Cells in a Model of Equine Tendonitis.. Stem Cells Int 2016;2016:8610964.
                  doi: 10.1155/2016/8610964pubmed: 27746821google scholar: lookup
                29. Metcalf GL, McClure SR, Hostetter JM, Martinez RF, Wang C. Evaluation of adipose-derived stromal vascular fraction from the lateral tailhead, inguinal region, and mesentery of horses.. Can J Vet Res 2016 Oct;80(4):294-301.
                  pubmed: 27733784
                30. Saeed H, Ahsan M, Saleem Z, Iqtedar M, Islam M, Danish Z, Khan AM. Mesenchymal stem cells (MSCs) as skeletal therapeutics - an update.. J Biomed Sci 2016 Apr 16;23:41.
                  doi: 10.1186/s12929-016-0254-3pubmed: 27084089google scholar: lookup
                31. Berner D, Brehm W, Gerlach K, Gittel C, Offhaus J, Paebst F, Scharner D, Burk J. Longitudinal Cell Tracking and Simultaneous Monitoring of Tissue Regeneration after Cell Treatment of Natural Tendon Disease by Low-Field Magnetic Resonance Imaging.. Stem Cells Int 2016;2016:1207190.
                  doi: 10.1155/2016/1207190pubmed: 26880932google scholar: lookup
                32. Maia L, da Cruz Landim-Alvarenga F, Taffarel MO, de Moraes CN, Machado GF, Melo GD, Amorim RM. Feasibility and safety of intrathecal transplantation of autologous bone marrow mesenchymal stem cells in horses.. BMC Vet Res 2015 Mar 15;11:63.
                  doi: 10.1186/s12917-015-0361-5pubmed: 25879519google scholar: lookup
                33. Sun HB, Schaniel C, Leong DJ, Wang JH. Biology and mechano-response of tendon cells: Progress overview and perspectives.. J Orthop Res 2015 Jun;33(6):785-92.
                  doi: 10.1002/jor.22885pubmed: 25728946google scholar: lookup
                34. Abbah SA, Spanoudes K, O'Brien T, Pandit A, Zeugolis DI. Assessment of stem cell carriers for tendon tissue engineering in pre-clinical models.. Stem Cell Res Ther 2014;5(2):38.
                  doi: 10.1186/scrt426pubmed: 25157898google scholar: lookup
                35. Zhao C, Ozasa Y, Reisdorf RL, Thoreson AR, Jay GD, An KN, Amadio PC. CORR® ORS Richard A. Brand Award for Outstanding Orthopaedic Research: Engineering flexor tendon repair with lubricant, cells, and cytokines in a canine model.. Clin Orthop Relat Res 2014 Sep;472(9):2569-78.
                  doi: 10.1007/s11999-014-3690-ypubmed: 24906811google scholar: lookup
                36. Machova Urdzikova L, Sedlacek R, Suchy T, Amemori T, Ruzicka J, Lesny P, Havlas V, Sykova E, Jendelova P. Human multipotent mesenchymal stem cells improve healing after collagenase tendon injury in the rat.. Biomed Eng Online 2014 Apr 9;13:42.
                  doi: 10.1186/1475-925X-13-42pubmed: 24712305google scholar: lookup
                37. Gittel C, Brehm W, Burk J, Juelke H, Staszyk C, Ribitsch I. Isolation of equine multipotent mesenchymal stromal cells by enzymatic tissue digestion or explant technique: comparison of cellular properties.. BMC Vet Res 2013 Oct 29;9:221.
                  doi: 10.1186/1746-6148-9-221pubmed: 24168625google scholar: lookup
                38. Giannotti S, Trombi L, Bottai V, Ghilardi M, D'Alessandro D, Danti S, Dell'Osso G, Guido G, Petrini M. Use of autologous human mesenchymal stromal cell/fibrin clot constructs in upper limb non-unions: long-term assessment.. PLoS One 2013;8(8):e73893.
                  doi: 10.1371/journal.pone.0073893pubmed: 24023694google scholar: lookup
                39. Xie L, Zhang N, Marsano A, Vunjak-Novakovic G, Zhang Y, Lopez MJ. In vitro mesenchymal trilineage differentiation and extracellular matrix production by adipose and bone marrow derived adult equine multipotent stromal cells on a collagen scaffold.. Stem Cell Rev Rep 2013 Dec;9(6):858-72.
                  doi: 10.1007/s12015-013-9456-1pubmed: 23892935google scholar: lookup
                40. Carvalho Ade M, Badial PR, Álvarez LE, Yamada AL, Borges AS, Deffune E, Hussni CA, Garcia Alves AL. Equine tendonitis therapy using mesenchymal stem cells and platelet concentrates: a randomized controlled trial.. Stem Cell Res Ther 2013 Jul 22;4(4):85.
                  doi: 10.1186/scrt236pubmed: 23876512google scholar: lookup
                41. Song N, Armstrong AD, Li F, Ouyang H, Niyibizi C. Multipotent mesenchymal stem cells from human subacromial bursa: potential for cell based tendon tissue engineering.. Tissue Eng Part A 2014 Jan;20(1-2):239-49.
                  doi: 10.1089/ten.TEA.2013.0197pubmed: 23865619google scholar: lookup
                42. Ruzzini L, Longo UG, Rizzello G, Denaro V. Stem cells and tendinopathy: state of the art from the basic science to clinic application.. Muscles Ligaments Tendons J 2012 Jul;2(3):235-8.
                  pubmed: 23738302
                43. Chaudhury S. Mesenchymal stem cell applications to tendon healing.. Muscles Ligaments Tendons J 2012 Jul;2(3):222-9.
                  pubmed: 23738300
                44. Tetta C, Consiglio AL, Bruno S, Tetta E, Gatti E, Dobreva M, Cremonesi F, Camussi G. The role of microvesicles derived from mesenchymal stem cells in tissue regeneration; a dream for tendon repair?. Muscles Ligaments Tendons J 2012 Jul;2(3):212-21.
                  pubmed: 23738299
                45. Volk SW, Theoret C. Translating stem cell therapies: the role of companion animals in regenerative medicine.. Wound Repair Regen 2013 May-Jun;21(3):382-94.
                  doi: 10.1111/wrr.12044pubmed: 23627495google scholar: lookup
                46. Reed SA, Johnson SE. Expression of scleraxis and tenascin C in equine adipose and umbilical cord blood derived stem cells is dependent upon substrata and FGF supplementation.. Cytotechnology 2014 Jan;66(1):27-35.
                  doi: 10.1007/s10616-012-9533-3pubmed: 23299298google scholar: lookup
                47. Janowski M, Bulte JW, Walczak P. Personalized nanomedicine advancements for stem cell tracking.. Adv Drug Deliv Rev 2012 Oct;64(13):1488-507.
                  doi: 10.1016/j.addr.2012.07.008pubmed: 22820528google scholar: lookup
                48. Delling U, Lindner K, Ribitsch I, Jülke H, Brehm W. Comparison of bone marrow aspiration at the sternum and the tuber coxae in middle-aged horses.. Can J Vet Res 2012 Jan;76(1):52-6.
                  pubmed: 22754095
                49. Young M. Stem cell applications in tendon disorders: a clinical perspective.. Stem Cells Int 2012;2012:637836.
                  doi: 10.1155/2012/637836pubmed: 22448174google scholar: lookup
                50. Gulotta LV, Chaudhury S, Wiznia D. Stem cells for augmenting tendon repair.. Stem Cells Int 2012;2012:291431.
                  doi: 10.1155/2012/291431pubmed: 22190960google scholar: lookup
                51. James R, Kumbar SG, Laurencin CT, Balian G, Chhabra AB. Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems.. Biomed Mater 2011 Apr;6(2):025011.
                  doi: 10.1088/1748-6041/6/2/025011pubmed: 21436509google scholar: lookup
                52. Fortier LA, Travis AJ. Stem cells in veterinary medicine.. Stem Cell Res Ther 2011 Feb 23;2(1):9.
                  doi: 10.1186/scrt50pubmed: 21371354google scholar: lookup
                53. Lovati AB, Corradetti B, Lange Consiglio A, Recordati C, Bonacina E, Bizzaro D, Cremonesi F. Comparison of equine bone marrow-, umbilical cord matrix and amniotic fluid-derived progenitor cells.. Vet Res Commun 2011 Feb;35(2):103-21.
                  doi: 10.1007/s11259-010-9457-3pubmed: 21193959google scholar: lookup
                54. Myers TJ, Granero-Molto F, Longobardi L, Li T, Yan Y, Spagnoli A. Mesenchymal stem cells at the intersection of cell and gene therapy.. Expert Opin Biol Ther 2010 Dec;10(12):1663-79.
                  doi: 10.1517/14712598.2010.531257pubmed: 21058931google scholar: lookup
                55. Koch TG, Berg LC, Betts DH. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine.. Can Vet J 2009 Feb;50(2):155-65.
                  pubmed: 19412395
                56. Violini S, Ramelli P, Pisani LF, Gorni C, Mariani P. Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12.. BMC Cell Biol 2009 Apr 22;10:29.
                  doi: 10.1186/1471-2121-10-29pubmed: 19383177google scholar: lookup
                57. Koch TG, Berg LC, Betts DH. Concepts for the clinical use of stem cells in equine medicine.. Can Vet J 2008 Oct;49(10):1009-17.
                  pubmed: 19119371