Analyze Diet
Animals : an open access journal from MDPI2023; 13(8); 1312; doi: 10.3390/ani13081312

Allogenic Synovia-Derived Mesenchymal Stem Cells for Treatment of Equine Tendinopathies and Desmopathies-Proof of Concept.

Abstract: Tendon and ligament injuries are frequent in sport horses and humans, and such injuries represent a significant therapeutic challenge. Tissue regeneration and function recovery are the paramount goals of tendon and ligament lesion management. Nowadays, several regenerative treatments are being developed, based on the use of stem cell and stem cell-based therapies. In the present study, the preparation of equine synovial membrane mesenchymal stem cells (eSM-MSCs) is described for clinical use, collection, transport, isolation, differentiation, characterization, and application. These cells are fibroblast-like and grow in clusters. They retain osteogenic, chondrogenic, and adipogenic differentiation potential. We present 16 clinical cases of tendonitis and desmitis, treated with allogenic eSM-MSCs and autologous serum, and we also include their evaluation, treatment, and follow-up. The concerns associated with the use of autologous serum as a vehicle are related to a reduced immunogenic response after the administration of this therapeutic combination, as well as the pro-regenerative effects from the growth factors and immunoglobulins that are part of its constitution. Most of the cases (14/16) healed in 30 days and presented good outcomes. Treatment of tendon and ligament lesions with a mixture of eSM-MSCs and autologous serum appears to be a promising clinical option for this category of lesions in equine patients.
Publication Date: 2023-04-11 PubMed ID: 37106875PubMed Central: PMC10135243DOI: 10.3390/ani13081312Google 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 explores the use of mesenchymal stem cells derived from horse’s synovial membrane tissues for the treatment of tendon and ligament injuries in equines, commonly known as tendonitis and desmitis. These conditions are also frequent problems in human sports medicine. The research indicates that these stem cells, combined with the patient’s own serum, offer positive results in healing injured tissues.

Study Methodology

  • The study began by preparing equine synovial membrane mesenchymal stem cells (eSM-MSCs) for clinical use. This included collection, transportation, isolation, differentiation, and characterization of the cells.
  • The eSM-MSCs were observed to have a fibroblast-like appearance and grew in clusters. These cells showed potential to differentiate into osteogenic, chondrogenic, and adipogenic lines, vital for tissue regeneration in tendon and ligament injuries.

Clinical Cases and Treatment

  • The study examined 16 clinical cases of tendonitis and desmitis. Each case was treated using allogenic eSM-MSCs (cells from a different horse) and autologous serum (serum from the same horse).
  • The treatment, evaluation, and follow-up of these cases were documented. The main concern of using autologous serum was the possibility of a reduced immune response after the administration of the treatment, and also the pro-regenerative effects of the growth factors and immunoglobulins that make up the serum’s constitution.

Results and Potential

  • Post treatment, most of the cases (14 out of 16 cases) showed successful healing within 30 days and exhibited favorable outcomes. This indicates the therapeutic potential of the eSM-MSC and autologous serum combination.
  • The study concludes that treating tendon or ligament injuries using a mixture of eSM-MSCs and autologous serum seems to be a promising clinical option for such lesions in equine patients. The findings might as well provide potential insight into human tendon and ligament injury therapies in the future.

Cite This Article

APA
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. (2023). Allogenic Synovia-Derived Mesenchymal Stem Cells for Treatment of Equine Tendinopathies and Desmopathies-Proof of Concept. Animals (Basel), 13(8), 1312. https://doi.org/10.3390/ani13081312

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 13
Issue: 8
PII: 1312

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, No. 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, No. 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, No. 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, No. 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
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 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.
  • University School Vasco da Gama (EUVG), Avenida José R. Sousa Fernandes, 3020-210 Coimbra, Portugal.
  • Vasco da Gama Research Center (CIVG), University School Vasco da Gama (EUVG), Avenida José R. Sousa Fernandes, 3020-210 Coimbra, Portugal.
Pedrosa, Sílvia Santos
  • 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.
  • Centro de Biotecnologia e Química Fina (CBQF), Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Rua de Diogo Botelho 1327, 4169-005 Porto, Portugal.
Rêma, Alexandra
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 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.
Oliveira, Cláudia
  • Laboratório de Citogenética, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal.
Porto, Beatriz
  • Laboratório de Citogenética, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal.
Atayde, Luís
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 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.
Amorim, Irina
  • Departamento de Patologia e Imunologia Molecular, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal.
  • Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto (UP), Rua Alfredo Allen, 4200-135 Porto, Portugal.
Alvites, Rui
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 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.
Santos, Jorge Miguel
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 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.
Maurício, Ana Colette
  • Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 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.

Grant Funding

  • SFRH/BD/146172/2019 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • SFRH/BD/146689/2019 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • 2021.05265.BD / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • UIDB/04044/2020 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • UIDB/00211/2020 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • PEst-OE/AGR/UI0211/2011 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • POCI-01-0247-FEDER-033877 / Agencia de Inovacao
  • POCI-01-0145-FEDER-031146 / Agencia de Inovacao

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 90 references
  1. Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases.. Animals (Basel) 2021 Jan 19;11(1).
    doi: 10.3390/ani11010234pmc: PMC7832834pubmed: 33477808google scholar: lookup
  2. 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
  3. Tuemmers C, Rebolledo N, Aguilera R. Effect of the application of stem cells for tendon injuries in sporting horses.. Arch. De Med. Vet. 2012;44:207–215.
  4. Platonova S, Korovina D, Viktorova E, Savchenkova I. Equine Tendinopathy Therapy Using Mesenchymal Stem Cells.. KnE Life Sci. 2021:533–541.
    doi: 10.18502/kls.v0i0.8987google scholar: lookup
  5. Chandra V, Mankuzhy P, Sharma G T. Mesenchymal Stem Cells in Veterinary Regenerative Therapy: Basic Physiology and Clinical Applications.. Curr Stem Cell Res Ther 2022;17(3):237-251.
  6. Depuydt E, Broeckx SY, Van Hecke L, Chiers K, Van Brantegem L, van Schie H, Beerts C, Spaas JH, Pille F, Martens A. The Evaluation of Equine Allogeneic Tenogenic Primed Mesenchymal Stem Cells in a Surgically Induced Superficial Digital Flexor Tendon Lesion Model.. Front Vet Sci 2021;8:641441.
    doi: 10.3389/fvets.2021.641441pmc: PMC7973085pubmed: 33748217google scholar: lookup
  7. Berebichez-Fridman R, Montero-Olvera PR. Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review.. Sultan Qaboos Univ Med J 2018 Aug;18(3):e264-e277.
  8. De Schauwer C, Meyer E, Van de Walle GR, Van Soom A. Markers of stemness in equine mesenchymal stem cells: a plea for uniformity.. Theriogenology 2011 May;75(8):1431-43.
  9. De Bari C, Dell'Accio F, Tylzanowski P, Luyten FP. Multipotent mesenchymal stem cells from adult human synovial membrane.. Arthritis Rheum 2001 Aug;44(8):1928-42.
  10. Harvanová D, Tóthová T, Sarišský M, Amrichová J, Rosocha J. Isolation and characterization of synovial mesenchymal stem cells.. Folia Biol (Praha) 2011;57(3):119-24.
    pubmed: 21888835
  11. Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source.. Arthritis Rheum 2005 Aug;52(8):2521-9.
    doi: 10.1002/art.21212pubmed: 16052568google scholar: lookup
  12. Shirasawa S, Sekiya I, Sakaguchi Y, Yagishita K, Ichinose S, Muneta T. In vitro chondrogenesis of human synovium-derived mesenchymal stem cells: optimal condition and comparison with bone marrow-derived cells.. J Cell Biochem 2006 Jan 1;97(1):84-97.
    doi: 10.1002/jcb.20546pubmed: 16088956google scholar: lookup
  13. Koga H, Muneta T, Ju YJ, Nagase T, Nimura A, Mochizuki T, Ichinose S, von der Mark K, Sekiya I. Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration.. Stem Cells 2007 Mar;25(3):689-96.
    doi: 10.1634/stemcells.2006-0281pubmed: 17138960google scholar: lookup
  14. Bami M, Sarlikiotis T, Milonaki M, Vikentiou M, Konsta E, Kapsimali V, Pappa V, Koulalis D, Johnson EO, Soucacos PN. Superiority of synovial membrane mesenchymal stem cells in chondrogenesis, osteogenesis, myogenesis and tenogenesis in a rabbit model.. Injury 2020 Dec;51(12):2855-2865.
    doi: 10.1016/j.injury.2020.03.022pubmed: 32201117google scholar: lookup
  15. Zayed M, Newby S, Misk N, Donnell R, Dhar M. Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration.. Stem Cells Int 2018;2018:1073705.
    doi: 10.1155/2018/1073705pmc: PMC6011062pubmed: 29977305google scholar: lookup
  16. Hermida-Gómez T, Fuentes-Boquete I, Gimeno-Longas MJ, Muiños-López E, Díaz-Prado S, de Toro FJ, Blanco FJ. Quantification of cells expressing mesenchymal stem cell markers in healthy and osteoarthritic synovial membranes.. J Rheumatol 2011 Feb;38(2):339-49.
    doi: 10.3899/jrheum.100614pubmed: 21078714google scholar: lookup
  17. Mochizuki T, Muneta T, Sakaguchi Y, Nimura A, Yokoyama A, Koga H, Sekiya I. Higher chondrogenic potential of fibrous synovium- and adipose synovium-derived cells compared with subcutaneous fat-derived cells: distinguishing properties of mesenchymal stem cells in humans.. Arthritis Rheum 2006 Mar;54(3):843-53.
    doi: 10.1002/art.21651pubmed: 16508965google scholar: lookup
  18. Fickert S, Fiedler J, Brenner RE. Identification, quantification and isolation of mesenchymal progenitor cells from osteoarthritic synovium by fluorescence automated cell sorting.. Osteoarthritis Cartilage 2003 Nov;11(11):790-800.
    doi: 10.1016/S1063-4584(03)00167-5pubmed: 14609532google scholar: lookup
  19. Prado AA, Favaron PO, da Silva LC, Baccarin RY, Miglino MA, Maria DA. Characterization of mesenchymal stem cells derived from the equine synovial fluid and membrane.. BMC Vet Res 2015 Nov 10;11:281.
    doi: 10.1186/s12917-015-0531-5pmc: PMC4640348pubmed: 26555093google scholar: lookup
  20. Chen Y-W. Chondrogenic Capacities of Equine Synovial Progenitor Populations.. Ph.D. Thesis. University of Illinois at Urbana-Champaign; Champaign, IL, USA: 2012.
  21. Colbath AC, Frisbie DD, Dow SW, Kisiday JD, McIlwraith CW, Goodrich LR. Equine models for the investigation of mesenchymal stem cell therapies in orthopaedic disease.. Oper. Tech. Sport. Med. 2017;25:41–49.
  22. Yu H, Cheng J, Shi W, Ren B, Zhao F, Shi Y, Yang P, Duan X, Zhang J, Fu X, Hu X, Ao Y. Bone marrow mesenchymal stem cell-derived exosomes promote tendon regeneration by facilitating the proliferation and migration of endogenous tendon stem/progenitor cells.. Acta Biomater 2020 Apr 1;106:328-341.
    doi: 10.1016/j.actbio.2020.01.051pubmed: 32027991google scholar: lookup
  23. González-González A, García-Sánchez D, Dotta M, Rodríguez-Rey JC, Pérez-Campo FM. Mesenchymal stem cells secretome: The cornerstone of cell-free regenerative medicine.. World J Stem Cells 2020 Dec 26;12(12):1529-1552.
    doi: 10.4252/wjsc.v12.i12.1529pmc: PMC7789121pubmed: 33505599google scholar: lookup
  24. Davidson EJ. Lameness Evaluation of the Athletic Horse.. Vet Clin North Am Equine Pract 2018 Aug;34(2):181-191.
    doi: 10.1016/j.cveq.2018.04.013pubmed: 30007446google scholar: lookup
  25. AAEP Horse Show Committee. Guide to Veterinary Services for Horse Shows.. American Association of Equine Practitioners; Lexington, KY, USA: 1999.
  26. Broeckx SY, Seys B, Suls M, Vandenberghe A, Mariën T, Adriaensen E, Declercq J, Van Hecke L, Braun G, Hellmann K, Spaas JH. Equine Allogeneic Chondrogenic Induced Mesenchymal Stem Cells Are an Effective Treatment for Degenerative Joint Disease in Horses.. Stem Cells Dev 2019 Mar 15;28(6):410-422.
    doi: 10.1089/scd.2018.0061pmc: PMC6441287pubmed: 30623737google scholar: lookup
  27. Alzola Domingo R, Riggs CM, Gardner DS, Freeman SL. Ultrasonographic scoring system for superficial digital flexor tendon injuries in horses: intra- and inter-rater variability.. Vet Rec 2017 Dec 16;181(24):655.
    doi: 10.1136/vr.104233pubmed: 29217766google scholar: lookup
  28. 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.2022.843131pmc: PMC8894652pubmed: 35252428google scholar: lookup
  29. Johnson SA, Donnell JR, Donnell AD, Frisbie DD. Retrospective analysis of lameness localisation in Western Performance Horses: A ten-year review.. Equine Vet J 2021 Nov;53(6):1150-1158.
    doi: 10.1111/evj.13397pubmed: 33617019google scholar: lookup
  30. Ehrle A, Lilge S, Clegg PD, Maddox TW. Equine flexor tendon imaging part 1: Recent developments in ultrasonography, with focus on the superficial digital flexor tendon.. Vet J 2021 Dec;278:105764.
    doi: 10.1016/j.tvjl.2021.105764pubmed: 34678500google scholar: lookup
  31. Iimori M, Tamura N, Seki K, Kasashima Y. Relationship between the ultrasonographic findings of suspected superficial digital flexor tendon injury and the prevalence of subsequent severe superficial digital flexor tendon injuries in Thoroughbred horses: a retrospective study.. J Vet Med Sci 2022 Feb 23;84(2):261-265.
    doi: 10.1292/jvms.21-0028pmc: PMC8920721pubmed: 34937842google scholar: lookup
  32. Mitchell R, DaSilva D, Rosenbaum C, Blikslager A, Edwards RB. Ultrasound findings in tendons and ligaments of lame sport horses competing or training in South Florida venues during the winter seasons of 2007 through 2016.. Equine Vet. Educ. 2021;33:306–309.
    doi: 10.1111/eve.13298google scholar: lookup
  33. Guest DJ, Dudhia J, Smith RKW, Roberts SJ, Conzemius M, Innes JF, Fortier LA, Meeson RL. Position Statement: Minimal Criteria for Reporting Veterinary and Animal Medicine Research for Mesenchymal Stromal/Stem Cells in Orthopedic Applications.. Front Vet Sci 2022;9:817041.
    doi: 10.3389/fvets.2022.817041pmc: PMC8936138pubmed: 35321059google scholar: lookup
  34. Thomopoulos S, Parks WC, Rifkin DB, Derwin KA. Mechanisms of tendon injury and repair.. J Orthop Res 2015 Jun;33(6):832-9.
    doi: 10.1002/jor.22806pmc: PMC4418182pubmed: 25641114google scholar: lookup
  35. 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.
  36. Kaneps AJ. Practical Rehabilitation and Physical Therapy for the General Equine Practitioner.. Vet Clin North Am Equine Pract 2016 Apr;32(1):167-80.
    doi: 10.1016/j.cveq.2015.12.001pubmed: 26898959google scholar: lookup
  37. Davidson EJ. Controlled Exercise in Equine Rehabilitation.. Vet Clin North Am Equine Pract 2016 Apr;32(1):159-65.
    doi: 10.1016/j.cveq.2015.12.012pubmed: 26898964google scholar: lookup
  38. Ortved KF. Regenerative Medicine and Rehabilitation for Tendinous and Ligamentous Injuries in Sport Horses.. Vet Clin North Am Equine Pract 2018 Aug;34(2):359-373.
    doi: 10.1016/j.cveq.2018.04.012pubmed: 29803299google scholar: lookup
  39. 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.
  40. Gale AL, Linardi RL, McClung G, Mammone RM, Ortved KF. Comparison of the Chondrogenic Differentiation Potential of Equine Synovial Membrane-Derived and Bone Marrow-Derived Mesenchymal Stem Cells.. Front Vet Sci 2019;6:178.
    doi: 10.3389/fvets.2019.00178pmc: PMC6562279pubmed: 31245393google scholar: lookup
  41. Zayed M, Adair S, Dhar M. Effects of Normal Synovial Fluid and Interferon Gamma on Chondrogenic Capability and Immunomodulatory Potential Respectively on Equine Mesenchymal Stem Cells.. Int J Mol Sci 2021 Jun 15;22(12).
    doi: 10.3390/ijms22126391pmc: PMC8232615pubmed: 34203758google scholar: lookup
  42. Murata D, Ishikawa S, Sunaga T, Saito Y, Sogawa T, Nakayama K, Hobo S, Hatazoe T. Osteochondral regeneration of the femoral medial condyle by using a scaffold-free 3D construct of synovial membrane-derived mesenchymal stem cells in horses.. BMC Vet Res 2022 Jan 22;18(1):53.
    doi: 10.1186/s12917-021-03126-ypmc: PMC8783486pubmed: 35065631google scholar: lookup
  43. Fülber J, Maria DA, da Silva LC, Massoco CO, Agreste F, Baccarin RY. Comparative study of equine mesenchymal stem cells from healthy and injured synovial tissues: an in vitro assessment.. Stem Cell Res Ther 2016 Mar 5;7:35.
    doi: 10.1186/s13287-016-0294-3pmc: PMC4779201pubmed: 26944403google scholar: lookup
  44. Peterson SE, Loring JF. Genomic instability in pluripotent stem cells: implications for clinical applications.. J Biol Chem 2014 Feb 21;289(8):4578-84.
    doi: 10.1074/jbc.R113.516419pmc: PMC3931019pubmed: 24362040google scholar: lookup
  45. Lupski JR. Genetics. Genome mosaicism--one human, multiple genomes.. Science 2013 Jul 26;341(6144):358-9.
    doi: 10.1126/science.1239503pubmed: 23888031google scholar: lookup
  46. Rohrback S, Siddoway B, Liu CS, Chun J. Genomic mosaicism in the developing and adult brain.. Dev Neurobiol 2018 Nov;78(11):1026-1048.
    doi: 10.1002/dneu.22626pmc: PMC6214721pubmed: 30027562google scholar: lookup
  47. Thorpe J, Osei-Owusu IA, Avigdor BE, Tupler R, Pevsner J. Mosaicism in Human Health and Disease.. Annu Rev Genet 2020 Nov 23;54:487-510.
  48. Vattathil S, Scheet P. Extensive Hidden Genomic Mosaicism Revealed in Normal Tissue.. Am J Hum Genet 2016 Mar 3;98(3):571-578.
    doi: 10.1016/j.ajhg.2016.02.003pmc: PMC4800050pubmed: 26942289google scholar: lookup
  49. Petropoulos M, Champeris Tsaniras S, Taraviras S, Lygerou Z. Replication Licensing Aberrations, Replication Stress, and Genomic Instability.. Trends Biochem Sci 2019 Sep;44(9):752-764.
    doi: 10.1016/j.tibs.2019.03.011pubmed: 31054805google scholar: lookup
  50. Prieto González E, Haider KH. Genomic Instability in Stem Cells: The Basic Issues. Springer; Berlin/Heidelberg, Germany: 2021; pp. 107–150.
  51. Neri S. Genetic Stability of Mesenchymal Stromal Cells for Regenerative Medicine Applications: A Fundamental Biosafety Aspect.. Int J Mol Sci 2019 May 15;20(10).
    doi: 10.3390/ijms20102406pmc: PMC6566307pubmed: 31096604google scholar: lookup
  52. 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/cells9061453pmc: PMC7349187pubmed: 32545382google scholar: lookup
  53. Madrigal M, Rao KS, Riordan NH. A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods.. J Transl Med 2014 Oct 11;12:260.
    doi: 10.1186/s12967-014-0260-8pmc: PMC4197270pubmed: 25304688google scholar: lookup
  54. 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
  55. Shireman PK, Contreras-Shannon V, Ochoa O, Karia BP, Michalek JE, McManus LM. MCP-1 deficiency causes altered inflammation with impaired skeletal muscle regeneration.. J Leukoc Biol 2007 Mar;81(3):775-85.
    doi: 10.1189/jlb.0506356pubmed: 17135576google scholar: lookup
  56. Theret M, Saclier M, Messina G, Rossi FMV. Macrophages in Skeletal Muscle Dystrophies, An Entangled Partner.. J Neuromuscul Dis 2022;9(1):1-23.
    pmc: PMC8842758pubmed: 34542080doi: 10.3233/jnd-210737google scholar: lookup
  57. Yang P, Wen H, Ou S, Cui J, Fan D. IL-6 promotes regeneration and functional recovery after cortical spinal tract injury by reactivating intrinsic growth program of neurons and enhancing synapse formation.. Exp Neurol 2012 Jul;236(1):19-27.
  58. Friese N, Gierschner MB, Schadzek P, Roger Y, Hoffmann A. Regeneration of Damaged Tendon-Bone Junctions (Entheses)-TAK1 as a Potential Node Factor.. Int J Mol Sci 2020 Jul 22;21(15).
    doi: 10.3390/ijms21155177pmc: PMC7432881pubmed: 32707785google scholar: lookup
  59. Brent AE, Tabin CJ. FGF acts directly on the somitic tendon progenitors through the Ets transcription factors Pea3 and Erm to regulate scleraxis expression.. Development 2004 Aug;131(16):3885-96.
    doi: 10.1242/dev.01275pubmed: 15253939google scholar: lookup
  60. Zhang YJ, Chen X, Li G, Chan KM, Heng BC, Yin Z, Ouyang HW. Concise Review: Stem Cell Fate Guided By Bioactive Molecules for Tendon Regeneration.. Stem Cells Transl Med 2018 May;7(5):404-414.
    doi: 10.1002/sctm.17-0206pmc: PMC5905226pubmed: 29573225google scholar: lookup
  61. Kobayashi Y, Kida Y, Kabuto Y, Morihara T, Sukenari T, Nakagawa H, Onishi O, Oda R, Kida N, Tanida T, Matsuda KI, Tanaka M, Takahashi K. Healing Effect of Subcutaneous Administration of Granulocyte Colony-Stimulating Factor on Acute Rotator Cuff Injury in a Rat Model.. Tissue Eng Part A 2021 Sep;27(17-18):1205-1212.
    doi: 10.1089/ten.tea.2020.0239.Apubmed: 34432525google scholar: lookup
  62. Wright CR, Ward AC, Russell AP. Granulocyte Colony-Stimulating Factor and Its Potential Application for Skeletal Muscle Repair and Regeneration.. Mediators Inflamm 2017;2017:7517350.
    doi: 10.1155/2017/7517350pmc: PMC5738577pubmed: 29362521google scholar: lookup
  63. Sakuma T, Yamazaki M, Okawa A, Takahashi H, Kato K, Hashimoto M, Hayashi K, Furuya T, Fujiyoshi T, Kawabe J, Mannoji C, Miyashita T, Kadota R, Someya Y, Ikeda O, Yamauchi T, Hashimoto M, Aizawa T, Ono A, Imagama S, Kanemura T, Hanaoka H, Takahashi K, Koda M. Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of thoracic myelopathy: a multicenter prospective controlled trial.. Spine (Phila Pa 1976) 2012 Aug 1;37(17):1475-8.
    doi: 10.1097/BRS.0b013e318260cc71pubmed: 22652593google scholar: lookup
  64. Yamazaki M, Sakuma T, Kato K, Furuya T, Koda M. Granulocyte colony-stimulating factor reduced neuropathic pain associated with thoracic compression myelopathy: report of two cases.. J Spinal Cord Med 2013 Jan;36(1):40-3.
  65. Kato K, Koda M, Takahashi H, Sakuma T, Inada T, Kamiya K, Ota M, Maki S, Okawa A, Takahashi K, Yamazaki M, Aramomi M, Hashimoto M, Ikeda O, Mannoji C, Furuya T. Granulocyte colony-stimulating factor attenuates spinal cord injury-induced mechanical allodynia in adult rats.. J Neurol Sci 2015 Aug 15;355(1-2):79-83.
    doi: 10.1016/j.jns.2015.05.024pubmed: 26055312google scholar: lookup
  66. Kamiya K, Koda M, Furuya T, Kato K, Takahashi H, Sakuma T, Inada T, Ota M, Maki S, Okawa A, Ito Y, Takahashi K, Yamazaki M. Neuroprotective therapy with granulocyte colony-stimulating factor in acute spinal cord injury: a comparison with high-dose methylprednisolone as a historical control.. Eur Spine J 2015 May;24(5):963-7.
    doi: 10.1007/s00586-014-3373-0pubmed: 24961222google scholar: lookup
  67. Kato K, Yamazaki M, Okawa A, Furuya T, Sakuma T, Takahashi H, Kamiya K, Inada T, Takahashi K, Koda M. Intravenous administration of granulocyte colony-stimulating factor for treating neuropathic pain associated with compression myelopathy: a phase I and IIa clinical trial.. Eur Spine J 2013 Jan;22(1):197-204.
    doi: 10.1007/s00586-012-2556-9pmc: PMC3540322pubmed: 23139012google scholar: lookup
  68. Okurowska-Zawada B, Kułak W, Sienkiewicz D, Paszko-Patej G, Dmitruk E, Kalinowska A, Wojtkowski J, Korzeniecka–Kozerska A. Safety and efficacy of granulocyte colony stimulating factor in a patient with tetraplegia caused by cervical hyperextension injury: A case report.. Prog. Health Sci. 2014;4:181–184.
  69. 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
  70. Shiomi A, Usui T. Pivotal roles of GM-CSF in autoimmunity and inflammation.. Mediators Inflamm 2015;2015:568543.
    doi: 10.1155/2015/568543pmc: PMC4370199pubmed: 25838639google scholar: lookup
  71. Paredes J, Marvin JC, 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 Jun;34(6):8341-8356.
    doi: 10.1096/fj.201902825RRpmc: PMC7478906pubmed: 32350938google scholar: lookup
  72. 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 Jul;1(3):68-76.
    pmc: PMC3666474pubmed: 23738251
  73. Ohls RK, Maheshwari A. Hematology, Immunology and Infectious Disease: Neonatology Questions and Controversies: Expert Consult-Online and Print.. Elsevier Health Sciences; Amsterdam, The Netherlands: 2012.
  74. Lai F, Wang J, Tang H, Huang P, Liu J, He G, Zhou M, Tao X, Tang K. VEGF promotes tendon regeneration of aged rats by inhibiting adipogenic differentiation of tendon stem/progenitor cells and promoting vascularization.. FASEB J 2022 Aug;36(8):e22433.
    doi: 10.1096/fj.202200213Rpubmed: 35867348google scholar: lookup
  75. Bussche L, Van de Walle GR. Peripheral Blood-Derived Mesenchymal Stromal Cells Promote Angiogenesis via Paracrine Stimulation of Vascular Endothelial Growth Factor Secretion in the Equine Model.. Stem Cells Transl Med 2014 Dec;3(12):1514-25.
    doi: 10.5966/sctm.2014-0138pmc: PMC4250216pubmed: 25313202google scholar: lookup
  76. Ranganath SH, Levy O, Inamdar MS, Karp JM. Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease.. Cell Stem Cell 2012 Mar 2;10(3):244-58.
    doi: 10.1016/j.stem.2012.02.005pmc: PMC3294273pubmed: 22385653google scholar: lookup
  77. 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;36:43–48.
    doi: 10.21836/PEM20200107google scholar: lookup
  78. Smith RK, Cauvin ER. Ultrasonography of the Metacarpus and Metatarsus. Wiley; Hoboken, NJ, USA: 2014; pp. 73–105.
  79. Cook JL, Evans R, Conzemius MG, Lascelles BD, McIlwraith CW, Pozzi A, Clegg P, Innes J, Schulz K, Houlton J, Fortier L, Cross AR, Hayashi K, Kapatkin A, Brown DC, Stewart A. Proposed definitions and criteria for reporting time frame, outcome, and complications for clinical orthopedic studies in veterinary medicine.. Vet Surg 2010 Dec;39(8):905-8.
  80. Khatab S, van Osch GJ, Kops N, Bastiaansen-Jenniskens YM, Bos PK, Verhaar JA, Bernsen MR, van Buul GM. Mesenchymal stem cell secretome reduces pain and prevents cartilage damage in a murine osteoarthritis model.. Eur Cell Mater 2018 Nov 6;36:218-230.
    doi: 10.22203/eCM.v036a16pubmed: 30398288google scholar: lookup
  81. Wang HN, Rong X, Yang LM, Hua WZ, Ni GX. Advances in Stem Cell Therapies for Rotator Cuff Injuries.. Front Bioeng Biotechnol 2022;10:866195.
    doi: 10.3389/fbioe.2022.866195pmc: PMC9174670pubmed: 35694228google scholar: lookup
  82. Beltrami AP, Cesselli D, Bergamin N, Marcon P, Rigo S, Puppato E, D'Aurizio F, Verardo R, Piazza S, Pignatelli A, Poz A, Baccarani U, Damiani D, Fanin R, Mariuzzi L, Finato N, Masolini P, Burelli S, Belluzzi O, Schneider C, Beltrami CA. Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow).. Blood 2007 Nov 1;110(9):3438-46.
    doi: 10.1182/blood-2006-11-055566pubmed: 17525288google scholar: lookup
  83. Riekstina U, Cakstina I, Parfejevs V, Hoogduijn M, Jankovskis G, Muiznieks I, Muceniece R, Ancans J. Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis.. Stem Cell Rev Rep 2009 Dec;5(4):378-86.
    doi: 10.1007/s12015-009-9094-9pubmed: 20058201google scholar: lookup
  84. Greco SJ, Liu K, Rameshwar P. Functional similarities among genes regulated by OCT4 in human mesenchymal and embryonic stem cells.. Stem Cells 2007 Dec;25(12):3143-54.
    doi: 10.1634/stemcells.2007-0351pubmed: 17761754google scholar: lookup
  85. Zhang S, Muneta T, Morito T, Mochizuki T, Sekiya I. Autologous synovial fluid enhances migration of mesenchymal stem cells from synovium of osteoarthritis patients in tissue culture system.. J Orthop Res 2008 Oct;26(10):1413-8.
    doi: 10.1002/jor.20659pubmed: 18418888google scholar: lookup
  86. Kamm JL, Riley CB, Parlane N, Gee EK, McIlwraith CW. Interactions Between Allogeneic Mesenchymal Stromal Cells and the Recipient Immune System: A Comparative Review With Relevance to Equine Outcomes.. Front Vet Sci 2020;7:617647.
    doi: 10.3389/fvets.2020.617647pmc: PMC7838369pubmed: 33521090google scholar: lookup
  87. Colbath AC, Dow SW, McIlwraith CW, Goodrich LR. Mesenchymal stem cells for treatment of musculoskeletal disease in horses: Relative merits of allogeneic versus autologous stem cells.. Equine Vet J 2020 Sep;52(5):654-663.
    doi: 10.1111/evj.13233pubmed: 31971273google scholar: lookup
  88. Li C, Zhao H, Cheng L, Wang B. Allogeneic vs. autologous mesenchymal stem/stromal cells in their medication practice.. Cell Biosci 2021 Nov 2;11(1):187.
    doi: 10.1186/s13578-021-00698-ypmc: PMC8561357pubmed: 34727974google scholar: lookup
  89. Galipeau J, Krampera M, Barrett J, Dazzi F, Deans RJ, DeBruijn J, Dominici M, Fibbe WE, Gee AP, Gimble JM, Hematti P, Koh MB, LeBlanc K, Martin I, McNiece IK, Mendicino M, Oh S, Ortiz L, Phinney DG, Planat V, Shi Y, Stroncek DF, Viswanathan S, Weiss DJ, Sensebe L. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials.. Cytotherapy 2016 Feb;18(2):151-9.
    doi: 10.1016/j.jcyt.2015.11.008pmc: PMC4745114pubmed: 26724220google scholar: lookup
  90. Lui PP, Maffulli N, Rolf C, Smith RK. What are the validated animal models for tendinopathy?. Scand J Med Sci Sports 2011 Feb;21(1):3-17.

Citations

This article has been cited 1 times.
  1. Gouveia D, Correia J, Cardoso A, Carvalho C, Oliveira AC, Almeida A, Gamboa Ó, Ribeiro L, Branquinho M, Sousa A, Lopes B, Sousa P, Moreira A, Coelho A, Rêma A, Alvites R, Ferreira A, Maurício AC, Martins Â. Intensive neurorehabilitation and allogeneic stem cells transplantation in canine degenerative myelopathy.. Front Vet Sci 2023;10:1192744.
    doi: 10.3389/fvets.2023.1192744pubmed: 37520009google scholar: lookup