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Frontiers in veterinary science2024; 11; 1282697; doi: 10.3389/fvets.2024.1282697

Safety assessment of equine allogeneic tenogenic primed mesenchymal stem cells in horses with naturally occurring tendon and ligament injuries.

Abstract: Mesenchymal stem cells provide a valuable treatment option in orthopedic injuries in horses. Unassigned: The aim of this study was to evaluate the hematological, biochemical, immunological and immunomodulatory parameters following intralesional treatment with tenogenic primed equine allogeneic peripheral blood-derived mesenchymal stem cells (tpMSCs) in client-owned horses with naturally occurring superficial digital flexor tendon (SDFT) and suspensory ligament (SL) injuries. Unassigned: The immunogenicity and immunomodulatory capacities of tpMSCs were assessed in a modified mixed lymphocyte reaction, including peripheral blood mononuclear cells (PBMCs) of 14 horses with SDFT and SL injuries after treatment with tpMSCs. In a second study, 18 horses with SDFT and SL injuries received either an intralesional injection with tpMSCs ( = 9) or no treatment ( = 9). Unassigned: The tpMSCs did not provoke a cellular immune response ( < 0.001) and were able to immunomodulate stimulated T lymphocytes ( < 0.001) . Therapeutic use of tpMSCs did not result in relevant hematologic or biochemical abnormalities. Unassigned: Both studies had a small sample size. No statistical analyses were performed in the second study. Fibrinogen was only analyzed in a single horse prior to treatment. Unassigned: Co-incubation of tpMSCs and PBMCs of horses that have been previously exposed to tpMSCs did not elicit a cellular immune response and tpMSCs were able to immunomodulate stimulated T lymphocytes. Intralesional treatment with tpMSCs did not provoke abnormal changes in hematological and biochemical parameters.
Copyright © 2024 Carlier, Depuydt, Van Hecke, Martens, Saunders and Spaas.
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Publication Date: 2024-02-26 PubMed ID: 38468694PubMed Central: PMC10925754DOI: 10.3389/fvets.2024.1282697Google Scholar: Lookup
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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 research article explores the safety and efficacy of using tenogenic primed mesenchymal stem cells (tpMSCs) in horses with tendon and ligament injuries. The researchers found that the tpMSCs safely influenced immune responses without causing abnormal changes in hematological or biochemical parameters.

Objective of the Study

The main aim of the study was to investigate the impact of tpMSCs on biochemical, immunological, hematological, and immunomodulatory functions in horses with naturally occurring injuries. The researchers were keen to assess the potential of these cells as a therapeutic tool in the treatment of superficial digital flexor tendon (SDFT) and suspensory ligament (SL) injuries.

  • The researchers tested the immunogenicity and immunomodulatory capacities of tpMSCs in a modified mixed lymphocyte reaction.
  • They used peripheral blood mononuclear cells (PBMCs) from 14 horses with either SDFT or SL injuries, treated with tpMSCs, for this part of the study.

Methodology and Findings

The researchers performed a second study, where they divided 18 horses with tendon and ligament injuries into two groups. One group received an intralesional injection with tpMSCs, while the other group was left untreated.

  • The key finding in this part of the study was that injecting tpMSCs did not trigger a cellular immune response.
  • Also, tpMSCs demonstrated the ability to influence or immunomodulate stimulated T lymphocytes.
  • Moreover, using tpMSCs did not lead to changes in hematologic or biochemical parameters, indicating their potential safety as a therapeutic tool.

Limitations

The study had a few limitations, which included:

  • It had a small sample size, which might limit the generalization of its findings.
  • No statistical analyses were performed in the second study, which could potentially affect the interpretation of the results.
  • Fibrinogen was only analyzed in a single horse prior to treatment, which might not give a comprehensive view of the effect of treatment on fibrinogen levels.

Conclusion

The study concluded that tpMSCs did not trigger a cellular immune response when used for treating tendon or ligament injuries in horses. Also, the use of these cells did not result in abnormal changes in hematological or biochemical parameters. These findings suggest that tpMSCs might be safe to use in treating similar conditions, but more comprehensive studies are needed to confirm these results.

Cite This Article

APA
Carlier S, Depuydt E, Van Hecke L, Martens A, Saunders J, Spaas JH. (2024). Safety assessment of equine allogeneic tenogenic primed mesenchymal stem cells in horses with naturally occurring tendon and ligament injuries. Front Vet Sci, 11, 1282697. https://doi.org/10.3389/fvets.2024.1282697

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 11
Pages: 1282697
PII: 1282697

Researcher Affiliations

Carlier, Stephanie
  • Stephanie Carlier, Kortrijk, Belgium.
  • Department of Large Animal Surgery, Anaesthesia and Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
  • Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Depuydt, Eva
  • Boehringer Ingelheim Veterinary Medicine Belgium, Evergem, Belgium.
Van Hecke, Lore
  • Boehringer Ingelheim Veterinary Medicine Belgium, Evergem, Belgium.
Martens, Ann
  • Department of Large Animal Surgery, Anaesthesia and Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Saunders, Jimmy
  • Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Spaas, Jan H
  • Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
  • Boehringer Ingelheim Animal Health USA, Athens, GA, United States.

Conflict of Interest Statement

SC, ED, LV, and JHS were employed by Boehringer-Ingelheim or an affiliated company at the time of the study. The content of this manuscript contains a commercially available stem cell product (RenuTend©) owned and patented by Boehringer-Ingelheim. The funder had the following involvement in the study: the studies were performed to collect additional data for Marketing Authorization. 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. One of the authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

References

This article includes 46 references
  1. Geburek F, Roggel F, Van Schie HTM, Beineke A, Estrada R, Weber K. 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) 8:129.
    doi: 10.1186/s13287-017-0564-8pmc: PMC5460527pubmed: 28583184google scholar: lookup
  2. Sloet Van Oldruitenborgh-Oosterbaan MM, Genzel W, van Weeren PR. A pilot study on factors influencing the career of Dutch sport horses. Equine Vet J (2010) 42:28–32.
    doi: 10.1111/j.2042-3306.2010.00251.xpubmed: 21058979google scholar: lookup
  3. Murray RC, Dyson SJ, Tranquille C, Adams V. Association of type of sport and performance level with anatomical site of orthopaedic injury diagnosis. Equine Vet J (2006) 38:411–6.
    doi: 10.1111/j.2042-3306.2006.tb05578.xpubmed: 17402457google scholar: lookup
  4. Williams RB, Harkins LS, Hammond CJ, Wood JLN. 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) 33:478–86.
    doi: 10.2746/042516401776254808pubmed: 11558743google scholar: lookup
  5. Johnston AS, Riggs CM, Cogger N, Benschop J, Rogers CW, Rosanowski SM. Using time-series analysis techniques to enhance the understanding of musculoskeletal injury in thoroughbred racehorses. Equine Vet J (2020) 52:699–708.
    doi: 10.1111/evj.13220pubmed: 31811658google scholar: lookup
  6. Dowling BA, Dart AJ, Hodgson DR, Smith RKW. Superficial digital flexor tendonitis in the horse. Equine Vet J (2000) 32:369–78.
    doi: 10.2746/042516400777591138pubmed: 11037257google scholar: lookup
  7. Smith RKW, Goodship AE. Tendon and ligament physiology. Equine Sports Med Surg (2004):130–51.
    doi: 10.1016/B978-0-7020-2671-3.50012-Xgoogle scholar: lookup
  8. 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) 42:871–90.
    doi: 10.1007/BF03262300pubmed: 22963225google scholar: lookup
  9. Ahrberg AB, Horstmeier C, Berner D, Brehm W, Gittel C, Hillmann A. Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model. BMC Musculoskelet Disord (2018) 19:230.
    doi: 10.1186/s12891-018-2163-ypmc: PMC6052633pubmed: 30021608google scholar: lookup
  10. Depuydt E, Broeckx SY, van Hecke L, Chiers K, van Brantegem L, van Schie H. The evaluation of equine allogeneic Tenogenic primed mesenchymal stem cells in a surgically induced superficial digital flexor tendon lesion model. Front Vet Sci (2021) 8:8.
    doi: 10.3389/fvets.2021.641441pmc: PMC7973085pubmed: 33748217google scholar: lookup
  11. Bosch G, Moleman M, Barneveld A, van Weeren PR, van Schie HTM. The effect of platelet-rich plasma on the neovascularization of surgically created equine superficial digital flexor tendon lesions. Scand J Med Sci Sports (2011) 21:554–61.
    doi: 10.1111/j.1600-0838.2009.01070.xpubmed: 20459479google scholar: lookup
  12. Bosch G, van Schie HTM, de Groot MW, Cadby JA, van de Lest CHA, Barneveld A. Effects of platelet-rich plasma on the quality of repair of mechanically induced core lesions in equine superficial digital flexor tendons: a placebo-controlled experimental study. J Orthop Res (2010) 28:211–7.
    doi: 10.1002/jor.20980pubmed: 19714688google scholar: lookup
  13. Geburek F, Gaus M, van Schie HTM, Rohn K, Stadler PM. Effect of intralesional platelet-rich plasma (PRP) treatment on clinical and ultrasonographic parameters in equine naturally occurring superficial digital flexor tendinopathies - a randomized prospective controlled clinical trial. BMC Vet Res (2016) 12:191.
    doi: 10.1186/s12917-016-0826-1pmc: PMC5015224pubmed: 27604193google scholar: lookup
  14. Gaesser AM, Underwood C, Linardi RL, Even KM, Reef VB, Shetye SS. Evaluation of autologous protein solution injection for treatment of superficial digital flexor tendonitis in an equine model. Front Vet Sci (2021) 8:8.
    doi: 10.3389/fvets.2021.697551pmc: PMC8287003pubmed: 34291103google scholar: lookup
  15. Frisbie DD, Smith RKW. Clinical update on the use of mesenchymal stem cells in equine orthopaedics. Equine Vet J (2010) 42:86–9.
    doi: 10.2746/042516409X477263pubmed: 20121921google scholar: lookup
  16. Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RKW. 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) 44:25–32.
    doi: 10.1111/j.2042-3306.2011.00363.xpubmed: 21615465google scholar: lookup
  17. Richardson LE, Dudhia J, Clegg PD, Smith R. Stem cells in veterinary medicine - attempts at regenerating equine tendon after injury. Trends Biotechnol (2007) 25:409–16.
    doi: 10.1016/j.tibtech.2007.07.009pubmed: 17692415google scholar: lookup
  18. del Bue M, Riccò S, Ramoni R, Conti V, Gnudi G, Grolli S. Equine adipose-tissue derived mesenchymal stem cells and platelet concentrates: their association in vitro and in vivo. Vet Res Commun (2008) 32:51–5.
    doi: 10.1007/s11259-008-9093-3pubmed: 18683070google scholar: lookup
  19. Bertolo A, Steffen F, Malonzo-Marty C, Stoyanov J. Canine mesenchymal stem cell potential and the importance of dog breed: implication for cell-based therapies. Cell Transplant (2015) 24:1969–80.
    doi: 10.3727/096368914X685294pubmed: 25375819google scholar: lookup
  20. Lee KS, Cha SH, Kang HW, Song JY, Lee KW, Ko KB. Effects of serial passage on the characteristics and chondrogenic differentiation of canine umbilical cord matrix derived mesenchymal stem cells. Asian-Australas J Anim Sci (2013) 26:588–95.
    doi: 10.5713/ajas.2012.12488pmc: PMC4093376pubmed: 25049827google scholar: lookup
  21. Spaas JH, Schauwer CD, Cornillie P, Meyer E, Soom AV, van de Walle GR. Culture and characterisation of equine peripheral blood mesenchymal stromal cells. Vet J (2013) 195:107–13.
    doi: 10.1016/j.tvjl.2012.05.006pubmed: 22717781google scholar: lookup
  22. Thorpe CT, Udeze CP, Birch HL, Clegg PD, Screen HRC. Capacity for sliding between tendon fascicles decreases with ageing in injury prone equine tendons: a possible mechanism for age-related tendinopathy?. Eur Cell Mater (2013) 25:48–60.
    doi: 10.22203/eCM.v025a04pubmed: 23300032google scholar: lookup
  23. Ribitsch I, Gueltekin S, Keith MF, Minichmair K, Peham C, Jenner F. Age-related changes of tendon fibril micro-morphology and gene expression. J Anat (2020) 236:688–700.
    doi: 10.1111/joa.13125pmc: PMC7083562pubmed: 31792963google scholar: lookup
  24. Broeckx S, Zimmerman M, Crocetti S, Suls M, Mariën T, Ferguson SJ. Regenerative therapies for equine degenerative joint disease: a preliminary study. PloS One (2014) 9:1–11.
    doi: 10.1371/journal.pone.0085917pmc: PMC3896436pubmed: 24465787google scholar: lookup
  25. Broeckx SY, Maes S, Martinello T, Aerts D, Chiers K, Mariën T. Equine epidermis: a source of epithelial-like stem/progenitor cells with in vitro and in vivo regenerative capacities. Stem Cell Develop (2013) 23:1134–48.
    doi: 10.1089/scd.2013.0203pubmed: 24368059google scholar: lookup
  26. Tan K, Zheng K, Li D, Lu H, Wang S, Sun X. Impact of adipose tissue or umbilical cord derived mesenchymal stem cells on the immunogenicity of human cord blood derived endothelial progenitor cells. PloS One (2017) 12:e0178624.
    doi: 10.1371/journal.pone.0178624pmc: PMC5451078pubmed: 28562647google scholar: lookup
  27. Schnabel L, Pezzanite LM, Antczak DF, Felippe MJB, Fortier LA. Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro. Stem Cell Res Ther (2014) 5:13.
    doi: 10.1186/scrt402pmc: PMC4055004pubmed: 24461709google scholar: lookup
  28. Carlier S, Depuydt E, Suls M, Bocqué C, Thys J, Vandenberghe A. Equine allogeneic tenogenic primed mesenchymal stem cells: a clinical field study in horses suffering from naturally occurring superficial digital flexor tendon and suspensory ligament injuries. Equine Vet J (2023).
    doi: 10.1111/evj.14008pubmed: 37847100google scholar: lookup
  29. 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
  30. Balan M, McCullough M, O’Brien PJ. Equine blood reticulocytes: reference intervals, physiological and pathological changes. Comp Clin Pathol (2019) 28:53–62.
    doi: 10.1007/s00580-018-2820-4google scholar: lookup
  31. Giordano A, Rossi G, Pieralisi C, Paltrinieri S. Evaluation of equine hemograms using the ADVIA 120 as compared with an impedance counter and manual differential count. Vet Clin Pathol (2008) 37:21–30.
    doi: 10.1111/j.1939-165X.2008.00012.xpubmed: 18366541google scholar: lookup
  32. Wang Y, Tian M, Wang F, Heng BC, Zhou J, Cai Z. Understanding the immunological mechanisms of mesenchymal stem cells in allogeneic transplantation: from the aspect of major histocompatibility complex class I. Stem Cell Develop (2019) 28:1141–50.
    doi: 10.1089/scd.2018.0256pubmed: 31215341google scholar: lookup
  33. Deuse T, Hu X, Gravina A, Wang D, Tediashvili G, De C. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol (2019) 37:252–8.
    doi: 10.1038/s41587-019-0016-3pmc: PMC6419516pubmed: 30778232google scholar: lookup
  34. Baraniak PR, McDevitt TC. Stem cell paracrine actions and tissue regeneration. Regen Med (2010) 5:121–43.
    doi: 10.2217/rme.09.74pmc: PMC2833273pubmed: 20017699google scholar: lookup
  35. Nöth U, Steinert AF, Tuan RS. Technology insight: adult mesenchymal stem cells for osteoarthritis therapy. Nat Clin Pract Rheumatol (2008) 4:371–80.
    doi: 10.1038/ncprheum0816pubmed: 18477997google scholar: lookup
  36. Weiss ARR, Dahlke MH. Immunomodulation by mesenchymal stem cells (MSCs): mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol (2019) 10:1191.
    doi: 10.3389/fimmu.2019.01191pmc: PMC6557979pubmed: 31214172google scholar: lookup
  37. Berglund AK, Long JM, Robertson JB, Schnabel LV. TGF-β2 reduces the cell-mediated immunogenicity of equine MHC-mismatched bone marrow-derived mesenchymal stem cells without altering immunomodulatory properties. Front Cell Dev Biol (2021) 9:628382.
    doi: 10.3389/fcell.2021.628382pmc: PMC7889809pubmed: 33614658google scholar: lookup
  38. Berglund AK, Fisher MB, Cameron KA, Poole EJ, Schnabel LV. Transforming growth factor-β2 downregulates major histocompatibility complex (MHC) I and MHC II surface expression on equine bone marrow-derived mesenchymal stem cells without altering other phenotypic cell surface markers. Front Vet Sci (2017) 4:272065.
    doi: 10.3389/fvets.2017.00084pmc: PMC5466990pubmed: 28660198google scholar: lookup
  39. Beerts C, Suls M, Broeckx SY, Seys B, Vandenberghe A, Declercq J. 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) 4:1–10.
    doi: 10.3389/fvets.2017.00158pmc: PMC5622984pubmed: 29018808google scholar: lookup
  40. van den Belt AJM, Keg PR, Dik KJ, Barneveld A. The correlation between the dose and distribution of Intratendinous fluid injections in the flexor tendons/ligaments of the horse. J Vet Med A Physiol Pathol Clin Med (1993) 40:713–9.
    doi: 10.1111/j.1439-0442.1993.tb00688.xpubmed: 8135078google scholar: lookup
  41. Southwood LL. Normal ranges for Hematology and Palsma chemistry and conversion table for units. Prac Guide to Equine Colic (2013):339–42.
    doi: 10.1002/9781118704783.app3google scholar: lookup
  42. Walsh KA. Proteins. Equine Hematol, Cytology, Clin Chem (2020):95–102.
    doi: 10.1002/9781119500186.ch8google scholar: lookup
  43. Tyler RD, Cowell RL, Meinkoth JH. Disorders and laboratory evaluation. Vet Clin Pathol Secrets (2004):51–60.
    doi: 10.1016/B978-1-56053-633-8.50014-0google scholar: lookup
  44. Mueller MM, Bomke B, Seifried E. Fresh frozen plasma in patients with disseminated intravascular coagulation or in patients with liver diseases. Thromb Res (2002) 107:S9–S17.
    doi: 10.1016/S0049-3848(02)00146-9pubmed: 12379287google scholar: lookup
  45. Sok D, Raval S, McKinney J, Drissi H, Mason A, Mautner K. NSAIDs reduce therapeutic efficacy of mesenchymal stromal cell therapy in a rodent model of posttraumatic osteoarthritis. Am J Sports Med (2022) 50:1389–98.
    doi: 10.1177/03635465221083610pubmed: 35420503google scholar: lookup
  46. Müller M, Raabe O, Addicks K, Wenisch S, Arnhold S. Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells. Cell Biol Int (2011) 35:235–48.
    doi: 10.1042/CBI20090211pubmed: 21087205google scholar: lookup

Citations

This article has been cited 4 times.
  1. 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
  2. Aeri A, Gorla M, Sharma GT. Veterinary Regenerative Medicine: The Evolving Role of Stem Cell-Based Therapies. Stem Cell Rev Rep 2025 Nov;21(8):2484-2510.
    doi: 10.1007/s12015-025-10963-zpubmed: 40900287google scholar: lookup
  3. Guest DJ, Roberts SJ. Editorial: Insights in veterinary regenerative medicine: 2023. Front Vet Sci 2024;11:1483576.
    doi: 10.3389/fvets.2024.1483576pubmed: 39315087google scholar: lookup
  4. Carmona JU, Carmona-Ramírez LH, López C. Platelet-Rich Plasma and Related Orthobiologics for the Treatment of Equine Musculoskeletal Disorders-A Bibliometric Analysis from 2000 to 2024. Vet Sci 2024 Aug 21;11(8).
    doi: 10.3390/vetsci11080385pubmed: 39195839google scholar: lookup
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