Analyze Diet
Frontiers in veterinary science2021; 8; 641441; doi: 10.3389/fvets.2021.641441

The Evaluation of Equine Allogeneic Tenogenic Primed Mesenchymal Stem Cells in a Surgically Induced Superficial Digital Flexor Tendon Lesion Model.

Abstract: Tendon injuries are very common in horses and jeopardize the athletic performance, and due to the high risk of reinjury may lead to early retirement. The use of mesenchymal stem cells for the treatment of equine tendon disease is widely investigated because of their regenerative potential. The objective of this study is to investigate the safety and efficacy of equine allogeneic tenogenic primed mesenchymal stem cells (tpMSCs) for the management of tendinitis in horses. A core lesion was surgically induced in the superficial digital flexor tendon of both forelimbs of eight horses. After 7 days, one forelimb was treated with tpMSCs, while the contralateral forelimb served as an intra-individual control and was treated with saline. A prescribed exercise program was started. All horses underwent a daily clinical evaluation throughout the entire study period of 112 days. Blood samples were taken at different time points for hematological and biochemical analysis. Tendon assessment, lameness examination, ultrasound assessment and ultrasound tissue characterization (UTC) were performed at regular time intervals. At the end of the study period, the superficial digital flexor tendons were evaluated macroscopically and histologically. No suspected or serious adverse events occurred during the entire study period. There was no difference in local effects including heat and pain to pressure between a single intralesional injection of allogeneic tpMSCs and a single intralesional injection with saline. A transient moderate local swelling was noted in the tpMSC treated limbs, which dissipated by day 11. Starting at a different time point depending on the parameter, a significant improvement was observed in the tpMSC treated limbs compared to the placebo for echogenicity score, fiber alignment score, anterior-posterior thickness of the tendon and echo type by UTC assessment. Immunohistochemistry 112 days post-injection revealed that the amount of collagen type I and Von Willebrand factor were significantly higher in the tendon tissue of the tpMSC group, while the amount of collagen type III and smooth muscle actin was significantly lower. Equine allogeneic tenogenic primed mesenchymal stem cells were shown to be well-tolerated and may be effective for the management of tendon injuries.
Publication Date: 2021-03-05 PubMed ID: 33748217PubMed Central: PMC7973085DOI: 10.3389/fvets.2021.641441Google 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.

The study investigates the use of a type of stem cell, called tenogenic primed mesenchymal stem cells (tpMSCs), in treating tendon injuries in horses. Researchers found that the treatment led to significant improvements in different parameters associated with tendon healing and function, and was also well tolerated by the horses.

Study Methodology

  • The study involved creating a superficial digital flexor tendon injury in both forelimbs of eight horses. After a week, one forelimb of each horse was treated using tpMSCs, and the other forelimb treated with saline as a control.
  • The horses were then subjected to a prescribed exercise program, and clinically evaluated daily for a total study period of 112 days.
  • Blood samples were taken periodically for analysis. Various assessments, such as examination for lameness, tendon evaluation, and ultrasound, were performed at regular intervals. At the end of the study, the tendons were evaluated macroscopically and histologically.

Findings of the Study

  • No serious or suspected adverse effects were observed throughout the research period. There were no significant differences in pain levels or local heat effects between the limbs treated with tpMSCs and those treated with saline.
  • A transient, moderate swelling was noted in the limbs treated with tpMSCs, which subsided by the 11th day.
  • Starting from different periods, depending on the parameter being observed, the limbs treated with tpMSCs showed significant improvement in terms of echogenicity score, fiber alignment, thickness of the tendon, and echo type.
  • At 112 days post-injection, the tpMSC-treated tendons showed higher amounts of collagen type I and Von Willebrand factor, which are beneficial for healing, and lower amounts of collagen type III and smooth muscle actin, which are often correlated with scar formation and poorer healing. This suggested that tpMSC treatment might prompt a more successful, efficient healing process.

Implications of the Study

  • The study demonstrates that equine allogeneic tpMSCs are well-tolerated and might be effective in the management of tendon injuries. Hence, tpMSC therapy could potentially reduce the risk of reinjury and facilitate a faster return to athletic performance for horses suffering from tendon diseases.

Cite This Article

APA
Depuydt E, Broeckx SY, Van Hecke L, Chiers K, Van Brantegem L, van Schie H, Beerts C, Spaas JH, Pille F, Martens A. (2021). The Evaluation of Equine Allogeneic Tenogenic Primed Mesenchymal Stem Cells in a Surgically Induced Superficial Digital Flexor Tendon Lesion Model. Front Vet Sci, 8, 641441. https://doi.org/10.3389/fvets.2021.641441

Publication

ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 8
Pages: 641441
PII: 641441

Researcher Affiliations

Depuydt, Eva
  • Global Stem cell Technology, Part of Boehringer Ingelheim, Evergem, Belgium.
  • Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Broeckx, Sarah Y
  • Global Stem cell Technology, Part of Boehringer Ingelheim, Evergem, Belgium.
Van Hecke, Lore
  • Global Stem cell Technology, Part of Boehringer Ingelheim, Evergem, Belgium.
Chiers, Koen
  • Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Van Brantegem, Leen
  • Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
van Schie, Hans
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
  • Department of Research and Development, UTC Imaging, Stein, Netherlands.
Beerts, Charlotte
  • Global Stem cell Technology, Part of Boehringer Ingelheim, Evergem, Belgium.
  • Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Spaas, Jan H
  • Global Stem cell Technology, Part of Boehringer Ingelheim, Evergem, Belgium.
  • Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Pille, Frederik
  • Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Martens, Ann
  • Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Conflict of Interest Statement

JS declares competing financial interests as shareholder in GST at the time of the study. SB, JS, ED, CB, and LH were all employed by GST at the time of the study. The content of this manuscript contains a stem cell product under development (Tendo-Cell® Plus) owned by GST and patented under the following numbers: EP13799605.4, CA2928122, US15/038,172. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 51 references
  1. Maffulli N, Wong J. Rupture of the Achilles and patellar tendons.. Clin Sports Med 2003 Oct;22(4):761-76.
    doi: 10.1016/S0278-5919(03)00009-7pubmed: 14560546google scholar: lookup
  2. Cassel M, Baur H, Hirschmüller A, Carlsohn A, Fröhlich K, Mayer F. Prevalence of Achilles and patellar tendinopathy and their association to intratendinous changes in adolescent athletes.. Scand J Med Sci Sports 2015 Jun;25(3):e310-8.
    doi: 10.1111/sms.12318pubmed: 25212527google scholar: lookup
  3. Williams RB, Harkins LS, Hammond CJ, Wood JL. Racehorse injuries, clinical problems and fatalities recorded on British racecourses from flat racing and National Hunt racing during 1996, 1997 and 1998.. Equine Vet J 2001 Sep;33(5):478-86.
    doi: 10.2746/042516401776254808pubmed: 11558743google scholar: lookup
  4. Lam KH, Parkin TD, Riggs CM, Morgan KL. Descriptive analysis of retirement of Thoroughbred racehorses due to tendon injuries at the Hong Kong Jockey Club (1992-2004).. Equine Vet J 2007 Mar;39(2):143-8.
    doi: 10.2746/042516407X159132pubmed: 17378443google scholar: lookup
  5. Dyson SJ. Medical management of superficial digital flexor tendonitis: a comparative study in 219 horses (1992-2000).. Equine Vet J 2004 Jul;36(5):415-9.
    doi: 10.2746/0425164044868422pubmed: 15253082google scholar: lookup
  6. O'Meara B, Bladon B, Parkin TD, Fraser B, Lischer CJ. An investigation of the relationship between race performance and superficial digital flexor tendonitis in the Thoroughbred racehorse.. Equine Vet J 2010 May;42(4):322-6.
  7. Kasashima Y, Takahashi T, Smith RK, Goodship AE, Kuwano A, Ueno T, Hirano S. Prevalence of superficial digital flexor tendonitis and suspensory desmitis in Japanese Thoroughbred flat racehorses in 1999.. Equine Vet J 2004 May;36(4):346-50.
    doi: 10.2746/0425164044890580pubmed: 15163043google scholar: lookup
  8. Pinchbeck GL, Clegg PD, Proudman CJ, Stirk A, Morgan KL, French NP. Horse injuries and racing practices in National Hunt racehorses in the UK: the results of a prospective cohort study.. Vet J 2004 Jan;167(1):45-52.
    doi: 10.1016/S1090-0233(03)00141-2pubmed: 14623150google scholar: lookup
  9. van den Belt AJ, Dik KJ, Barneveld A. Ultrasonographic evaluation and long-term follow-up of flexor tendonitis/desmitis in the metacarpal/metatarsal region in Dutch warmblood horses and standardbred racehorses.. Vet Q 1994 May;16 Suppl 2:S76-80.
    doi: 10.1080/01652176.1994.9694507pubmed: 7801507google scholar: lookup
  10. Singer ER, Barnes J, Saxby F, Murray JK. Injuries in the event horse: training versus competition.. Vet J 2008 Jan;175(1):76-81.
    doi: 10.1016/j.tvjl.2006.11.009pubmed: 17204438google scholar: lookup
  11. Nichols AEC, Best KT, Loiselle AE. The cellular basis of fibrotic tendon healing: challenges and opportunities.. Transl Res 2019 Jul;209:156-168.
    doi: 10.1016/j.trsl.2019.02.002pmc: PMC6545261pubmed: 30776336google scholar: lookup
  12. James R, Kesturu G, Balian G, Chhabra AB. Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options.. J Hand Surg Am 2008 Jan;33(1):102-12.
    doi: 10.1016/j.jhsa.2007.09.007pubmed: 18261674google scholar: lookup
  13. Spaas JH, Guest DJ, Van de Walle GR. Tendon regeneration in human and equine athletes: Ubi Sumus-Quo Vadimus (where are we and where are we going to)?. Sports Med 2012 Oct 1;42(10):871-90.
    doi: 10.1007/BF03262300pubmed: 22963225google scholar: lookup
  14. Shojaee A, Parham A. Strategies of tenogenic differentiation of equine stem cells for tendon repair: current status and challenges.. Stem Cell Res Ther 2019 Jun 18;10(1):181.
    doi: 10.1186/s13287-019-1291-0pmc: PMC6582602pubmed: 31215490google scholar: lookup
  15. Maffulli N, Kader D. Tendinopathy of tendo achillis.. J Bone Joint Surg Br 2002 Jan;84(1):1-8.
  16. Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RK. 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 2012 Jan;44(1):25-32.
  17. Muttini A, Russo V, Rossi E, Mattioli M, Barboni B, Tosi U, Maffulli N, Valbonetti L, Abate M. Pilot experimental study on amniotic epithelial mesenchymal cell transplantation in natural occurring tendinopathy in horses. Ultrasonographic and histological comparison.. Muscles Ligaments Tendons J 2015 Jan-Mar;5(1):5-11.
    doi: 10.32098/mltj.01.2015.02pmc: PMC4396678pubmed: 25878980google scholar: lookup
  18. Ricco S, Renzi S, Del Bue M, Conti V, Merli E, Ramoni R, Lucarelli E, Gnudi G, Ferrari M, Grolli S. Allogeneic adipose tissue-derived mesenchymal stem cells in combination with platelet rich plasma are safe and effective in the therapy of superficial digital flexor tendonitis in the horse.. Int J Immunopathol Pharmacol 2013 Jan-Mar;26(1 Suppl):61-8.
    doi: 10.1177/03946320130260S108pubmed: 24046950google scholar: lookup
  19. Torricelli P, Fini M, Filardo G, Tschon M, Pischedda M, Pacorini A, Kon E, Giardino R. Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses.. Int Orthop 2011 Oct;35(10):1569-76.
    doi: 10.1007/s00264-011-1237-3pmc: PMC3174295pubmed: 21394594google scholar: lookup
  20. Crovace A, Lacitignola L, Rossi G, Francioso E. 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;2010:250978.
    doi: 10.4061/2010/250978pmc: PMC2859019pubmed: 20445779google scholar: lookup
  21. Romero A, Barrachina L, Ranera B, Remacha AR, Moreno B, de Blas I, Sanz A, Vázquez FJ, Vitoria A, Junquera C, Zaragoza P, Rodellar C. Comparison of autologous bone marrow and adipose tissue derived mesenchymal stem cells, and platelet rich plasma, for treating surgically induced lesions of the equine superficial digital flexor tendon.. Vet J 2017 Jun;224:76-84.
    doi: 10.1016/j.tvjl.2017.04.005pubmed: 28697880google scholar: lookup
  22. 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/ijms19092549pmc: PMC6163784pubmed: 30154348google scholar: lookup
  23. 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/s13287-017-0564-8pmc: PMC5460527pubmed: 28583184google scholar: lookup
  24. Dressler MR, Butler DL, Boivin GP. Effects of age on the repair ability of mesenchymal stem cells in rabbit tendon.. J Orthop Res 2005 Mar;23(2):287-93.
    doi: 10.1016/j.orthres.2004.06.017pubmed: 15734238google scholar: lookup
  25. Fang Z, Zhu T, Shen WL, Tang QM, Chen JL, Yin Z, Ji JF, Heng BC, Ouyang HW, Chen X. Transplantation of fetal instead of adult fibroblasts reduces the probability of ectopic ossification during tendon repair.. Tissue Eng Part A 2014 Jul;20(13-14):1815-26.
    doi: 10.1089/ten.tea.2013.0296pmc: PMC4086799pubmed: 24410299google scholar: lookup
  26. Harris MT, Butler DL, Boivin GP, Florer JB, Schantz EJ, Wenstrup RJ. Mesenchymal stem cells used for rabbit tendon repair can form ectopic bone and express alkaline phosphatase activity in constructs.. J Orthop Res 2004 Sep;22(5):998-1003.
    doi: 10.1016/j.orthres.2004.02.012pubmed: 15304271google scholar: lookup
  27. Gomiero C, Bertolutti G, Martinello T, Van Bruaene N, Broeckx SY, Patruno M, Spaas JH. Tenogenic induction of equine mesenchymal stem cells by means of growth factors and low-level laser technology.. Vet Res Commun 2016 Mar;40(1):39-48.
    doi: 10.1007/s11259-016-9652-ypubmed: 26757735google scholar: lookup
  28. Broeckx S. Tenogenesis of equine peripheral blood-derived mesenchymal stem cells: in vitro versus in vivo. J Tissue Sci Eng (2012) S11:1–6.
    doi: 10.4172/2157-7552.S11-001google scholar: lookup
  29. Beerts C, Suls M, Broeckx SY, Seys B, Vandenberghe A, Declercq J, Duchateau L, Vidal MA, Spaas JH. Tenogenically Induced Allogeneic Peripheral Blood Mesenchymal Stem Cells in Allogeneic Platelet-Rich Plasma: 2-Year Follow-up after Tendon or Ligament Treatment in Horses.. Front Vet Sci 2017;4:158.
    doi: 10.3389/fvets.2017.00158pmc: PMC5622984pubmed: 29018808google scholar: lookup
  30. Spaas JH, De Schauwer C, Cornillie P, Meyer E, Van Soom A, Van de Walle GR. Culture and characterisation of equine peripheral blood mesenchymal stromal cells.. Vet J 2013 Jan;195(1):107-13.
    doi: 10.1016/j.tvjl.2012.05.006pubmed: 22717781google scholar: lookup
  31. Schramme M, Hunter S, Campbell N, Blikslager A, Smith R. A surgical tendonitis model in horses: technique, clinical, ultrasonographic and histological characterisation.. Vet Comp Orthop Traumatol 2010;23(4):231-9.
    doi: 10.3415/VCOT-09-10-0106pubmed: 20585715google scholar: lookup
  32. Bosch G, René van Weeren P, Barneveld A, van Schie HT. Computerised analysis of standardised ultrasonographic images to monitor the repair of surgically created core lesions in equine superficial digital flexor tendons following treatment with intratendinous platelet rich plasma or placebo.. Vet J 2011 Jan;187(1):92-8.
    doi: 10.1016/j.tvjl.2009.10.014pubmed: 19932036google scholar: lookup
  33. Bosch G, Moleman M, Barneveld A, van Weeren PR, van Schie HT. The effect of platelet-rich plasma on the neovascularization of surgically created equine superficial digital flexor tendon lesions.. Scand J Med Sci Sports 2011 Aug;21(4):554-61.
  34. van Schie HT, Bakker EM, Cherdchutham W, Jonker AM, van de Lest CH, van Weeren PR. Monitoring of the repair process of surgically created lesions in equine superficial digital flexor tendons by use of computerized ultrasonography.. Am J Vet Res 2009 Jan;70(1):37-48.
    doi: 10.2460/ajvr.70.1.37pubmed: 19119947google scholar: lookup
  35. Movin T, Gad A, Reinholt FP, Rolf C. Tendon pathology in long-standing achillodynia. Biopsy findings in 40 patients.. Acta Orthop Scand 1997 Apr;68(2):170-5.
    doi: 10.3109/17453679709004002pubmed: 9174456google scholar: lookup
  36. Birch HL, Bailey AJ, Goodship AE. Macroscopic 'degeneration' of equine superficial digital flexor tendon is accompanied by a change in extracellular matrix composition.. Equine Vet J 1998 Nov;30(6):534-9.
  37. Cadby JA, David F, van de Lest C, Bosch G, van Weeren PR, Snedeker JG, van Schie HT. Further characterisation of an experimental model of tendinopathy in the horse.. Equine Vet J 2013 Sep;45(5):642-8.
    doi: 10.1111/evj.12035pubmed: 23448172google scholar: lookup
  38. 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.
    pmc: PMC2629419pubmed: 19412395
  39. Obaid H, Connell D. Cell therapy in tendon disorders: what is the current evidence?. Am J Sports Med 2010 Oct;38(10):2123-32.
    doi: 10.1177/0363546510373574pubmed: 20699425google scholar: lookup
  40. Constable PD, Hinchcliff KW, Done SH, Grünberg WB. Diseases of the alimentary tract. Veterinary Medicine 11th ed. (Missouri: Elsevier; ) (2017). 175–435.
  41. Shokry M, Mostafo A, Tohamy A, El-Sharkawi M. Autologous mesenchymal stem cells for treatment of acute superficial digital flexor tendonitis in athletic horses-A clinical study of 1 5 cases. Pferdeheilkunde (2020) 36:43–8.
    doi: 10.21836/PEM20200107google scholar: lookup
  42. Ahrberg AB, Horstmeier C, Berner D, Brehm W, Gittel C, Hillmann A, Josten C, Rossi G, Schubert S, Winter K, Burk J. Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model.. BMC Musculoskelet Disord 2018 Jul 18;19(1):230.
    doi: 10.1186/s12891-018-2163-ypmc: PMC6052633pubmed: 30021608google scholar: lookup
  43. Smith RK, Werling NJ, Dakin SG, Alam R, Goodship AE, Dudhia J. Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy.. PLoS One 2013;8(9):e75697.
  44. van Schie HT, Bakker EM, Jonker AM, van Weeren PR. Ultrasonographic tissue characterization of equine superficial digital flexor tendons by means of gray level statistics.. Am J Vet Res 2000 Feb;61(2):210-9.
    doi: 10.2460/ajvr.2000.61.210pubmed: 10685695google scholar: lookup
  45. Khan KM, Forster BB, Robinson J, Cheong Y, Louis L, Maclean L, Taunton JE. Are ultrasound and magnetic resonance imaging of value in assessment of Achilles tendon disorders? A two year prospective study.. Br J Sports Med 2003 Apr;37(2):149-53.
    doi: 10.1136/bjsm.37.2.149pmc: PMC1724608pubmed: 12663358google scholar: lookup
  46. Cadby JA, Buehler E, Godbout C, van Weeren PR, Snedeker JG. Differences between the cell populations from the peritenon and the tendon core with regard to their potential implication in tendon repair.. PLoS One 2014;9(3):e92474.
  47. Williams IF, Heaton A, McCullagh KG. Cell morphology and collagen types in equine tendon scar.. Res Vet Sci 1980 May;28(3):302-10.
    doi: 10.1016/S0034-5288(18)32713-9pubmed: 7414083google scholar: lookup
  48. Hinz B. Formation and function of the myofibroblast during tissue repair.. J Invest Dermatol 2007 Mar;127(3):526-37.
    doi: 10.1038/sj.jid.5700613pubmed: 17299435google scholar: lookup
  49. Kvist M, Józsa L, Järvinen M, Kvist H. Fine structural alterations in chronic Achilles paratenonitis in athletes.. Pathol Res Pract 1985 Oct;180(4):416-23.
    doi: 10.1016/S0344-0338(85)80115-1pubmed: 4070072google scholar: lookup
  50. Conze P, van Schie HT, van Weeren R, Staszyk C, Conrad S, Skutella T, Hopster K, Rohn K, Stadler P, Geburek F. Effect of autologous adipose tissue-derived mesenchymal stem cells on neovascularization of artificial equine tendon lesions.. Regen Med 2014;9(6):743-57.
    doi: 10.2217/rme.14.55pubmed: 25431911google scholar: lookup
  51. Durgam SS, Stewart AA, Sivaguru M, Wagoner Johnson AJ, Stewart MC. Tendon-derived progenitor cells improve healing of collagenase-induced flexor tendinitis.. J Orthop Res 2016 Dec;34(12):2162-2171.
    doi: 10.1002/jor.23251pubmed: 27035120google scholar: lookup

Citations

This article has been cited 11 times.
  1. Leal Reis I, Lopes B, Sousa P, Sousa AC, Branquinho M, Caseiro AR, Pedrosa SS, Rêma A, Oliveira C, Porto B, Atayde L, Amorim I, Alvites R, Santos JM, Maurício AC. Allogenic Synovia-Derived Mesenchymal Stem Cells for Treatment of Equine Tendinopathies and Desmopathies-Proof of Concept. Animals (Basel) 2023 Apr 11;13(8).
    doi: 10.3390/ani13081312pubmed: 37106875google scholar: lookup
  2. Franini A, Entani MG, Colosio E, Melotti L, Patruno M. Case report: Flexor carpi ulnaris tendinopathy in a lure-coursing dog treated with three platelet-rich plasma and platelet lysate injections. Front Vet Sci 2023;10:1003993.
    doi: 10.3389/fvets.2023.1003993pubmed: 36742986google scholar: lookup
  3. Zhang G, Zhou X, Hu S, Jin Y, Qiu Z. Large animal models for the study of tendinopathy. Front Cell Dev Biol 2022;10:1031638.
    doi: 10.3389/fcell.2022.1031638pubmed: 36393858google scholar: lookup
  4. Knott LE, Fonseca-Martinez BA, O'Connor AM, Goodrich LR, McIlwraith CW, Colbath AC. Current use of biologic therapies for musculoskeletal disease: A survey of board-certified equine specialists. Vet Surg 2022 May;51(4):557-567.
    doi: 10.1111/vsu.13805pubmed: 35383972google scholar: lookup
  5. Depuydt E, Broeckx SY, Chiers K, Patruno M, Da Dalt L, Duchateau L, Saunders J, Pille F, Martens A, Van Hecke L, Spaas JH. Cellular and Humoral Immunogenicity Investigation of Single and Repeated Allogeneic Tenogenic Primed Mesenchymal Stem Cell Treatments in Horses Suffering From Tendon Injuries. Front Vet Sci 2021;8:789293.
    doi: 10.3389/fvets.2021.789293pubmed: 35281431google scholar: lookup
  6. Melotti L, Carolo A, Elshazly N, Boesso F, Da Dalt L, Gabai G, Perazzi A, Iacopetti I, Patruno M. Case Report: Repeated Intralesional Injections of Autologous Mesenchymal Stem Cells Combined With Platelet-Rich Plasma for Superficial Digital Flexor Tendon Healing in a Show Jumping Horse. Front Vet Sci 2022;9:843131.
    doi: 10.3389/fvets.2022.843131pubmed: 35252428google scholar: lookup
  7. Zhang Z, Yang Y, Ma Y, Mai Z, Fu H, Wang X, Cao X, Li T, Li J, Guo Q. Clinical Diagnosis, Treatment, and Outcome Analysis of a Horse with Proximal Sesamoid Bone Fracture Complicated by Flexor Tendinitis. Vet Sci 2026 Jan 2;13(1).
    doi: 10.3390/vetsci13010040pubmed: 41600695google scholar: lookup
  8. Najeb M, Samy A, Rizk A, Mosbah E, Karrouf G. Regenerative biologics modulating inflammation and promoting tenogenesis in equine superficial digital flexor tendonitis: from molecular pathways to clinical translation. Ir Vet J 2025 Sep 17;78(1):21.
    doi: 10.1186/s13620-025-00309-zpubmed: 40963139google scholar: lookup
  9. Koch DW, Froneberger A, Berglund A, Connard S, Souther A, Schnabel LV. IL-1β + TGF-β2 dual-licensed mesenchymal stem cells have reduced major histocompatibility class I expression and positively modulate tenocyte migration, metabolism, and gene expression. J Am Vet Med Assoc 2024 Jun 1;262(S1):S61-S72.
    doi: 10.2460/javma.23.12.0708pubmed: 38547589google scholar: lookup
  10. Carlier S, Depuydt E, Van Hecke L, Martens A, Saunders J, Spaas JH. Safety assessment of equine allogeneic tenogenic primed mesenchymal stem cells in horses with naturally occurring tendon and ligament injuries. Front Vet Sci 2024;11:1282697.
    doi: 10.3389/fvets.2024.1282697pubmed: 38468694google scholar: lookup
  11. Burk J, Wittenberg-Voges L, Schubert S, Horstmeier C, Brehm W, Geburek F. Treatment of Naturally Occurring Tendon Disease with Allogeneic Multipotent Mesenchymal Stromal Cells: A Randomized, Controlled, Triple-Blinded Pilot Study in Horses. Cells 2023 Oct 24;12(21).
    doi: 10.3390/cells12212513pubmed: 37947591google scholar: lookup