Analyze Diet
Animals : an open access journal from MDPI2024; 14(3); doi: 10.3390/ani14030370

Treatment of Equine Tarsus Long Medial Collateral Ligament Desmitis with Allogenic Synovial Membrane Mesenchymal Stem/Stromal Cells Enhanced by Umbilical Cord Mesenchymal Stem/Stromal Cell-Derived Conditioned Medium: Proof of Concept.

Abstract: Horses are high-performance athletes prone to sportive injuries such as tendonitis and desmitis. The formation of fibrous tissue in tendon repair remains a challenge to overcome. This impels regenerative medicine to develop innovative therapies that enhance regeneration, retrieving original tissue properties. Multipotent Mesenchymal Stem/Stromal Cells (MSCs) have been successfully used to develop therapeutic products, as they secrete a variety of bioactive molecules that play a pivotal role in tissue regeneration. These factors are released in culture media for producing a conditioned medium (CM). The aforementioned assumptions led to the formulation of equine synovial membrane MSCs (eSM-MSCs)-the cellular pool that naturally regenerates joint tissue-combined with a medium enriched in immunomodulatory factors (among other bioactive factors) produced by umbilical cord stroma-derived MSCs (eUC-MSCs) that naturally contribute to suppressing the immune rejection in the maternal-fetal barrier. A description of an equine sport horse diagnosed with acute tarsocrural desmitis and treated with this formulation is presented. Ultrasonographic ligament recovery occurred in a reduced time frame, reducing stoppage time and allowing for the horse's return to unrestricted competition after the completion of a physical rehabilitation program. This study focused on the description of the therapeutic formulation and potential in an equine desmitis treatment using the cells themselves and their secretomes.
Publication Date: 2024-01-24 PubMed ID: 38338013PubMed Central: PMC10854557DOI: 10.3390/ani14030370Google 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 examined how donkey sperm can activate horse egg cells and lead to the development of mule embryos in vitro, using a method called Intracytoplasmic Sperm Injection (ICSI). The results showed distinct patterns in how key proteins are located in donkey sperm in comparison to horse sperm, and donkey sperm demonstrated a lower capability to activate pig egg cells. However, donkey sperm was capable of activating horse egg cells, resulting in the successful in vitro development of mule embryos.

Objective and Methods

  • The research aimed to understand better the potential for in vitro production of mule embryos, specifically using donkey sperm to fertilize horse egg cells.
  • It focused on the role of a key protein in sperm cells called Phospholipase C zeta (PLCζ) and its role in pronuclear formation and recruitment activities.
  • The process of Intracytoplasmic Sperm Injection (ICSI), where a single sperm is directly injected into an egg cell, was used to determine the ability of donkey sperm to activate horse egg cells. This was compared with the ability of horse sperm.

Results and Findings

  • Researchers observed different patterns of PLCζ localization in donkey sperm compared with horse sperm. PLCζ is involved in the process of activating egg cells after fertilization and plays a significant role in embryo development.
  • The ability of donkey sperm to activate pig egg cells was found to be lower than that of horse sperm. This suggests that there might be species-specific differences in how sperm cells can activate eggs.
  • However, when it came to the activation of horse egg cells, donkey sperm performed more effectively. This was observable by the successful in vitro production of mule embryos, with no significant differences in the development of the embryo stages compared to horse embryos produced using horse sperm.
  • This finding suggests that despite exhibiting differences in activating egg cells from other species (in this case, pigs), donkey sperm is capable of efficiently fertilizing and activating horse egg cells, leading to the successful development of mule embryos in vitro.

Implications and Future Research

  • The results of the study provide valuable insights into the interspecies fertility capabilities of equids, specifically when it comes to the production of mule embryos in vitro.
  • The findings could have important implications for the techniques used in horse breeding and for further advances in in vitro fertilization processes in equids. They also form a basis for further research on interspecies reproductive capabilities.

Cite This Article

APA
Leal Reis I, Lopes B, Sousa P, Sousa AC, Branquinho MV, Caseiro AR, Rêma A, Briote I, Mendonça CM, Santos JM, Atayde LM, Alvites RD, Maurício AC. (2024). Treatment of Equine Tarsus Long Medial Collateral Ligament Desmitis with Allogenic Synovial Membrane Mesenchymal Stem/Stromal Cells Enhanced by Umbilical Cord Mesenchymal Stem/Stromal Cell-Derived Conditioned Medium: Proof of Concept. Animals (Basel), 14(3). https://doi.org/10.3390/ani14030370

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 14
Issue: 3

Researcher Affiliations

Leal Reis, Inês
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
  • Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Avenida Central de Gandra 1317, 4585-116 Gandra, Portugal.
Lopes, Bruna
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
Sousa, Patrícia
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
Sousa, Ana Catarina
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
Branquinho, Mariana V
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
Caseiro, Ana Rita
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
  • Departamento de Ciências Veterinárias, Escola Universitária Vasco da Gama (EUVG), Avenida José R. Sousa Fernandes, Lordemão, 3020-210 Coimbra, Portugal.
  • Centro de Investigação Vasco da Gama (CIVG), Escola Universitária Vasco da Gama (EUVG), Avenida José R. Sousa Fernandes, Lordemão, 3020-210 Coimbra, Portugal.
Rêma, Alexandra
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
Briote, Inês
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
  • Campus Agrário de Vairão, Centro Clínico de Equinos de Vairão (CCEV), Rua da Braziela n° 100, 4485-144 Vairão, Portugal.
Mendonça, Carla M
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
  • Campus Agrário de Vairão, Centro Clínico de Equinos de Vairão (CCEV), Rua da Braziela n° 100, 4485-144 Vairão, Portugal.
Santos, Jorge Miguel
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
Atayde, Luís M
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
  • Campus Agrário de Vairão, Centro Clínico de Equinos de Vairão (CCEV), Rua da Braziela n° 100, 4485-144 Vairão, Portugal.
Alvites, Rui D
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
  • Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Avenida Central de Gandra 1317, 4585-116 Gandra, Portugal.
Maurício, Ana Colette
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
  • Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
  • Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal.
  • Campus Agrário de Vairão, Centro Clínico de Equinos de Vairão (CCEV), Rua da Braziela n° 100, 4485-144 Vairão, Portugal.

Grant Funding

  • MC-04/17; MC-18-2021 / Prémios Santa Casa Neurociências
  • UIDB/00211/2020 / Fundação para a Ciência e Tecnologia
  • 2022.04501.PTDC / Fundação para a Ciência e Tecnologia
  • SFRH/BD/146689/2019 / Fundação para a Ciência e Tecnologia
  • 2021.05265.BD / Fundação para a Ciência e Tecnologia
  • 2023.00246.BD / Fundação para a Ciência e Tecnologia

Conflict of Interest Statement

The authors declare that there are no conflicts of interest regarding the publication of this article.

References

This article includes 58 references
  1. Ortved K.F.. Regenerative medicine and rehabilitation for tendinous and ligamentous injuries in sport horses.. Vet. Clin. Equine Pract. 2018;34:359–373.
    doi: 10.1016/j.cveq.2018.04.012pubmed: 29803299google scholar: lookup
  2. Duddy H., Schoonover M., Hague B.. Outcome following local injection of a liquid amnion allograft for treatment of equine tendonitis or desmitis—100 cases.. BMC Vet. Res. 2022;18:391.
    doi: 10.1186/s12917-022-03480-5pmc: PMC9639279pubmed: 36345002google scholar: lookup
  3. Bramlage L.R.. Traumatic and developmental lesions of the tarsus.. Proc. Am. Assoc. Equine Pract. 2006;52:1–4.
  4. Stashak T.S.. Adams’ Lameness in Horses.. Verlag M. & H. Schaper; Alfeld, Germany: 2008.
  5. Lamb L., Zubrod C., Hague B., Brakenhoff J., Major M.. Clinical outcome of collateral ligament injuries of the tarsus.. Can. Vet. J. 2012;53:518.
    pmc: PMC3327590pubmed: 23115364
  6. Tokateloff N., Carmalt J., Manning S.. Trauma resulting in hemarthrosis and long medial collateral ligament desmitis of the tarsocrural joint in a horse.. Can. Vet. J. 2011;52:519.
    pmc: PMC3078006pubmed: 22043073
  7. Dik K.J.. Ultrasonography of the equine tarsus.. Vet. Radiol. Ultrasound. 1993;34:36–43.
  8. Bell C., Torske K., Lobb B.. Collateral ligament reconstruction in two horses following traumatic avulsion fracture using a knotless suture anchor construct.. Equine Vet. Educ. 2018;30:360–366.
    doi: 10.1111/eve.12683google scholar: lookup
  9. Fraschetto C., Dancot M., Vandersmissen M., Denoix J.-M., Coudry V.. Conservative management of equine tarsal collateral ligament injuries may allow return to normal performance.. J. Am. Vet. Med. Assoc. 2023;261:995–1003.
    doi: 10.2460/javma.22.12.0597pubmed: 37040895google scholar: lookup
  10. Bogatcheva N., Coleman M.. Conditioned medium of mesenchymal stromal cells: A new class of therapeutics.. Biochemistry. 2019;84:1375–1389.
    doi: 10.1134/S0006297919110129pubmed: 31760924google scholar: lookup
  11. Harrell C.R., Fellabaum C., Jovicic N., Djonov V., Arsenijevic N., Volarevic V.. Molecular mechanisms responsible for therapeutic potential of mesenchymal stem cell-derived secretome.. Cells. 2019;8:467.
    doi: 10.3390/cells8050467pmc: PMC6562906pubmed: 31100966google scholar: lookup
  12. Maguire G.. Stem cell therapy without the cells.. Commun. Integr. Biol. 2013;6:e26631.
    doi: 10.4161/cib.26631pmc: PMC3925653pubmed: 24567776google scholar: lookup
  13. Wu X., Jiang J., Gu Z., Zhang J., Chen Y., Liu X.. Mesenchymal stromal cell therapies: Immunomodulatory properties and clinical progress.. Stem Cell Res. Ther. 2020;11:345.
    doi: 10.1186/s13287-020-01855-9pmc: PMC7414268pubmed: 32771052google scholar: lookup
  14. Dominici M., Le Blanc K., Mueller I., Slaper-Cortenbach I., Marini F., Krause D., Deans R., Keating A., Prockop D., Horwitz E.. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.. Cytotherapy. 2006;8:315–317.
    doi: 10.1080/14653240600855905pubmed: 16923606google scholar: lookup
  15. Prockop D.J., Oh J.Y.. Medical therapies with adult stem/progenitor cells (MSCs): A backward journey from dramatic results in vivo to the cellular and molecular explanations.. J. Cell. Biochem. 2012;113:1460–1469.
    doi: 10.1002/jcb.24046pmc: PMC4147853pubmed: 22213121google scholar: lookup
  16. Caplan A.I.. Mesenchymal stem cells: Time to change the name!. Stem Cells Transl. Med. 2017;6:1445–1451.
    doi: 10.1002/sctm.17-0051pmc: PMC5689741pubmed: 28452204google scholar: lookup
  17. Richardson S.M., Kalamegam G., Pushparaj P.N., Matta C., Memic A., Khademhosseini A., Mobasheri R., Poletti F.L., Hoyland J.A., Mobasheri A.. Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration.. Methods. 2016;99:69–80.
    doi: 10.1016/j.ymeth.2015.09.015pubmed: 26384579google scholar: lookup
  18. Scala M., Lenarduzzi S., Spagnolo F., Trapasso M., Ottonello C., Muraglia A., Barla A., Strada P.. Regenerative medicine for the treatment of Teno-desmic injuries of the equine. A series of 150 horses treated with platelet-derived growth factors.. In Vivo. 2014;28:1119–1123.
    pubmed: 25398809
  19. Mocchi M., Dotti S., Del Bue M., Villa R., Bari E., Perteghella S., Torre M.L., Grolli S.. Veterinary regenerative medicine for musculoskeletal disorders: Can mesenchymal stem/stromal cells and their secretome be the new frontier?. Cells. 2020;9:1453.
    doi: 10.3390/cells9061453pmc: PMC7349187pubmed: 32545382google scholar: lookup
  20. Madrigal M., Rao K.S., Riordan N.H.. A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods.. J. Transl. Med. 2014;12:260.
    doi: 10.1186/s12967-014-0260-8pmc: PMC4197270pubmed: 25304688google scholar: lookup
  21. 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;16:301–322.
    doi: 10.1007/s12015-019-09932-0pubmed: 31797146google scholar: lookup
  22. Han C., Sun X., Liu L., Jiang H., Shen Y., Xu X., Li J., Zhang G., Huang J., Lin Z.. Exosomes and their therapeutic potentials of stem cells.. Stem Cells Int. 2016;2016:7653489.
    doi: 10.1155/2016/7653489pmc: PMC4684885pubmed: 26770213google scholar: lookup
  23. Pawitan J.A.. Prospect of stem cell conditioned medium in regenerative medicine.. BioMed Res. Int. 2014;2014:65849.
    doi: 10.1155/2014/965849pmc: PMC4229962pubmed: 25530971google scholar: lookup
  24. Li J.J., Hosseini-Beheshti E., Grau G.E., Zreiqat H., Little C.B.. Stem cell-derived extracellular vesicles for treating joint injury and osteoarthritis.. Nanomaterials. 2019;9:261.
    doi: 10.3390/nano9020261pmc: PMC6409698pubmed: 30769853google scholar: lookup
  25. Sun D.Z., Abelson B., Babbar P., Damaser M.S.. Harnessing the mesenchymal stem cell secretome for regenerative urology.. Nat. Rev. Urol. 2019;16:363–375.
    doi: 10.1038/s41585-019-0169-3pmc: PMC7027199pubmed: 30923338google scholar: lookup
  26. Raik S., Kumar A., Bhattacharyya S.. Insights into cell-free therapeutic approach: Role of stem cell “soup-ernatant”.. Biotechnol. Appl. Biochem. 2018;65:104–118.
    doi: 10.1002/bab.1561pubmed: 28321921google scholar: lookup
  27. Markov A., Thangavelu L., Aravindhan S., Zekiy A.O., Jarahian M., Chartrand M.S., Pathak Y., Marofi F., Shamlou S., Hassanzadeh A.. Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders.. Stem Cell Res. Ther. 2021;12:192.
    doi: 10.1186/s13287-021-02265-1pmc: PMC7971361pubmed: 33736695google scholar: lookup
  28. Leal Reis I., Lopes B., Sousa P., Sousa A.C., Branquinho M., Caseiro A.R., Pedrosa S.S., Rêma A., Oliveira C., Porto B.. Allogenic Synovia-Derived Mesenchymal Stem Cells for Treatment of Equine Tendinopathies and Desmopathies—Proof of Concept.. Animals. 2023;13:1312.
    doi: 10.3390/ani13081312pmc: PMC10135243pubmed: 37106875google scholar: lookup
  29. Bami M., Sarlikiotis T., Milonaki M., Vikentiou M., Konsta E., Kapsimali V., Pappa V., Koulalis D., Johnson E.O., Soucacos P.N.. Superiority of synovial membrane mesenchymal stem cells in chondrogenesis, osteogenesis, myogenesis and tenogenesis in a rabbit model.. Injury. 2020;51:2855–2865.
    doi: 10.1016/j.injury.2020.03.022pubmed: 32201117google scholar: lookup
  30. De Bari C., Dell’Accio F., Tylzanowski P., Luyten F.P.. Multipotent mesenchymal stem cells from adult human synovial membrane.. Arthritis Rheum. 2001;44:1928–1942.
  31. Yea J.-H., Kim Y., Jo C.H.. Comparison of mesenchymal stem cells from bone marrow, umbilical cord blood, and umbilical cord tissue in regeneration of a full-thickness tendon defect in vitro and in vivo.. Biochem. Biophys. Rep. 2023;34:101486.
  32. Partan R.U., Putra K.M., Kusuma N.F., Darma S., Reagan M., Muthia P., Radiandina A.S., Saleh M.I., Salim E.M.. Umbilical Cord Mesenchymal Stem Cell Secretome Improves Clinical Outcomes and Changes Biomarkers in Knee Osteoarthritis.. J. Clin. Med. 2023;12:7138.
    doi: 10.3390/jcm12227138pmc: PMC10672370pubmed: 38002750google scholar: lookup
  33. Chouw A., Sartika C.R., Milanda T., Faried A.. Interleukins profiling in umbilical cord mesenchymal stem cell-derived secretome.. Stem Cells Cloning Adv. Appl. 2022;15:1–9.
    doi: 10.2147/SCCAA.S356763pmc: PMC9015105pubmed: 35444427google scholar: lookup
  34. AAEP Horse Show Committee. Guide to Veterinary Services for Horse Shows.. 7th ed. American Association of Equine Practitioners; Lexington, KY, USA: 1999.
  35. Thomopoulos S., Parks W.C., Rifkin D.B., Derwin K.A.. Mechanisms of tendon injury and repair.. J. Orthop. Res. 2015;33:832–839.
    doi: 10.1002/jor.22806pmc: PMC4418182pubmed: 25641114google scholar: lookup
  36. Schils S., Turner T.. Review of early mobilization of muscle, tendon, and ligament after injury in equine rehabilitation. Proceedings of the 56th Annual Convention of the American Association of Equine Practitioners; Baltimore, MD, USA. 4–8 December 2010; pp. 374–380.
  37. Kaneps A.J.. Practical rehabilitation and physical therapy for the general equine practitioner.. Vet. Clin. Equine Pract. 2016;32:167–180.
    doi: 10.1016/j.cveq.2015.12.001pubmed: 26898959google scholar: lookup
  38. Davidson E.J.. Controlled exercise in equine rehabilitation.. Vet. Clin. Equine Pract. 2016;32:159–165.
    doi: 10.1016/j.cveq.2015.12.012pubmed: 26898964google scholar: lookup
  39. Sherlock C., Eggleston R., Peroni J., Parks A.. Desmitis of the medial tarsal collateral ligament in 7 horses.. Equine Vet. Educ. 2012;24:72–80.
  40. Fan J., Varshney R.R., Ren L., Cai D., Wang D.-A.. Synovium-derived mesenchymal stem cells: A new cell source for musculoskeletal regeneration.. Tissue Eng. Part B Rev. 2009;15:75–86.
    doi: 10.1089/ten.teb.2008.0586pubmed: 19196118google scholar: lookup
  41. Murata D., Miyakoshi D., Hatazoe T., Miura N., Tokunaga S., Fujiki M., Nakayama K., Misumi K.. Multipotency of equine mesenchymal stem cells derived from synovial fluid.. Vet. J. 2014;202:53–61.
    doi: 10.1016/j.tvjl.2014.07.029pubmed: 25151209google scholar: lookup
  42. Nagamura-Inoue T., He H.. Umbilical cord-derived mesenchymal stem cells: Their advantages and potential clinical utility.. World J. Stem Cells. 2014;6:195.
    doi: 10.4252/wjsc.v6.i2.195pmc: PMC3999777pubmed: 24772246google scholar: lookup
  43. Zhang Y.-J., Chen X., Li G., Chan K.-M., Heng B.C., Yin Z., Ouyang H.-W.. Concise review: Stem cell fate guided by bioactive molecules for tendon regeneration.. Stem Cells Transl. Med. 2018;7:404–414.
    doi: 10.1002/sctm.17-0206pmc: PMC5905226pubmed: 29573225google scholar: lookup
  44. Shiomi A., Usui T., Mimori T.. GM-CSF as a therapeutic target in autoimmune diseases.. Inflamm. Regen. 2016;36:8.
    doi: 10.1186/s41232-016-0014-5pmc: PMC5725926pubmed: 29259681google scholar: lookup
  45. Wright C.R., Ward A.C., Russell A.P.. Granulocyte colony-stimulating factor and its potential application for skeletal muscle repair and regeneration.. Mediat. Inflamm. 2017;2017:7517350.
    doi: 10.1155/2017/7517350pmc: PMC5738577pubmed: 29362521google scholar: lookup
  46. Paredes J., Marvin J.C., Vaughn B., Andarawis-Puri N.. Innate tissue properties drive improved tendon healing in MRL/MpJ and harness cues that enhance behavior of canonical healing cells.. FASEB J. 2020;34:8341–8356.
    doi: 10.1096/fj.201902825RRpmc: PMC7478906pubmed: 32350938google scholar: lookup
  47. Al-Sadi O., Schulze-Tanzil G., Kohl B., Lohan A., Lemke M., Ertel W., John T.. Tenocytes, pro-inflammatory cytokines and leukocytes: A relationship?. Muscles Ligaments Tendons J. 2011;1:68.
    pmc: PMC3666474pubmed: 23738251
  48. Abumaree M., Al Jumah M., Pace R.A., Kalionis B.. Immunosuppressive properties of mesenchymal stem cells.. Stem Cell Rev. Rep. 2012;8:375–392.
    doi: 10.1007/s12015-011-9312-0pubmed: 21892603google scholar: lookup
  49. Hofer H.R., Tuan R.S.. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies.. Stem Cell Res. Ther. 2016;7:131.
    doi: 10.1186/s13287-016-0394-0pmc: PMC5016979pubmed: 27612948google scholar: lookup
  50. Galun E., Rose-John S.. The regenerative activity of interleukin-6.. Tissue-Prot. Cytokines Methods Protoc. 2013:59–77.
    doi: 10.1007/978-1-62703-308-4_4pubmed: 23456862google scholar: lookup
  51. Hirota H., Kiyama H., Kishimoto T., Taga T.. Accelerated Nerve Regeneration in Mice by upregulated expression of interleukin (IL) 6 and IL-6 receptor after trauma.. J. Exp. Med. 1996;183:2627–2634.
    doi: 10.1084/jem.183.6.2627pmc: PMC2192614pubmed: 8676083google scholar: lookup
  52. Ackermann P.W., Domeij-Arverud E., Leclerc P., Amoudrouz P., Nader G.. Anti-inflammatory cytokine profile in early human tendon repair.. Knee Surg. Sports Traumatol. Arthrosc. 2013;21:1801–1806.
    doi: 10.1007/s00167-012-2197-xpubmed: 22983752google scholar: lookup
  53. Chen S., Deng G., Li K., Zheng H., Wang G., Yu B., Zhang K.. Interleukin-6 promotes proliferation but inhibits tenogenic differentiation via the Janus kinase/signal transducers and activators of transcription 3 (JAK/STAT3) pathway in tendon-derived stem cells.. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2018;24:1567.
    doi: 10.12659/MSM.908802pmc: PMC5868364pubmed: 29547593google scholar: lookup
  54. Lin T.W., Cardenas L., Glaser D.L., Soslowsky L.J.. Tendon healing in interleukin-4 and interleukin-6 knockout mice.. J. Biomech. 2006;39:61–69.
  55. Andersen M.B., Pingel J., Kjær M., Langberg H.. Interleukin-6: A growth factor stimulating collagen synthesis in human tendon.. J. Appl. Physiol. 2011;110:1549–1554.
  56. Kim K.-O., Sim J.A., Choi J.U., Lee B.K., Park H.G.. The effect of interleukin-8 in the early stage after anterior cruciate ligament reconstruction with remnant preservation.. Knee Surg. Relat. Res. 2020;32:5.
    doi: 10.1186/s43019-019-0024-0pmc: PMC7219225pubmed: 32660594google scholar: lookup
  57. Ohls R.K., Maheshwari A.. Hematology, Immunology and Infectious Disease: Neonatology Questions and Controversies: Expert Consult-Online and Print.. Elsevier Health Sciences; London, UK: 2012.
  58. Amable P.R., Teixeira M.V.T., Carias R.B.V., Granjeiro J.M., Borojevic R.. Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton’s jelly.. Stem Cell Res. Ther. 2014;5:53.
    doi: 10.1186/scrt442pmc: PMC4055160pubmed: 24739658google scholar: lookup