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Veterinary medicine international2021; 2021; 5024905; doi: 10.1155/2021/5024905

Effect of Allogeneic Oral Mucosa Mesenchymal Stromal Cells on Equine Wound Repair.

Abstract: To assess the clinical value and safety of the application of allogeneic equine oral mucosa mesenchymal stromal cells (OM-MSCs) to wounds. Animals. 8 healthy adult horses without front limb skin lesions or musculoskeletal disease. Procedures. Stem cells were isolated from the oral mucosa of a donor horse. Horses were subjected to the creation of eight full-thickness cutaneous wounds, two on each distal forelimb (FL) and two on both sides of the thorax (TH). Each wound was subjected to one out of four treatments: no medication (T1), hyaluronic acid- (HA-) gel containing OM-MSC (T2), HA-gel containing OM-MSC secretome (T3), and HA-gel alone (T4). Gross macroscopic evaluation and laser digital photographic documentation were regularly performed to allow wound assessment including wound surface area. Full-thickness skin punch biopsy was performed at each site before wound induction (D0, normal skin) and after complete wound healing (D62, repaired skin). Results: All wounds healed without adverse effect at D62. Distal limb wounds are slower to heal than body wounds. OM-MSC and its secretome have a positive impact on TH wound contraction. OM-MSC has a positive impact on the contraction and epithelialization of FL wounds. No significant difference between wound sites before and after treatment was noted at histological examination. Conclusion and Clinical Relevance. Using horse cells harvested from oral mucosa is a feasible technique to produce OM-MSC or its secretome. The gel produced by the combination of these biologic components with HA shows a positive impact when applied during the early stage of wound healing.
Publication Date: 2021-12-14 PubMed ID: 34950446PubMed Central: PMC8692048DOI: 10.1155/2021/5024905Google Scholar: Lookup
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  • Journal Article

Summary

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This research investigates the use of allogeneic equine oral mucosa mesenchymal stromal cells and their secretome in the treatment of wounds in horses, identifying promising results for wound contraction and epithelialization, without any notable adverse effects.

Research Methods and Methodology

  • The researchers used healthy adult horses with no front limb skin conditions or musculoskeletal disease for the study.
  • Stem cells were isolated from the oral mucosa of a donor horse. These are specialized cells that have the potential to develop into different cell types in the body.
  • Each horse was subjected to eight full-thickness cutaneous wounds, two on their distal forelimb (FL) and two on both sides of the thorax (TH).
  • Each wound was then subjected to one of four treatments: non-treated (T1), treatment with a hyaluronic acid– (HA-) gel containing oral mucosa mesenchymal stromal cells (OM-MSC; T2), treatment with an HA-gel containing OM-MSC secretome (T3), and HA-gel alone (T4).
  • They undertook macroscopic evaluations and laser digital photographic documentation for wound assessment, including evaluation of the wound surface area. Full-thickness skin punch biopsy was performed at each site before the wound induction (D0, normal skin) and after complete wound healing (D62, repaired skin).

Results

  • All the wounds healed without any adverse effects by D62.
  • Wounds located on the distal limb healed slower than those on the body.
  • OM-MSCs and their secretome had a positive effect on thorax wound contraction.
  • OM-MSCs also positively influenced the contraction and epithelialization of forelimb wounds.
  • No significant difference was observed between the wound sites before and after the treatment upon histological examination.

Conclusions

  • The use of cells harvested from the horse’s oral mucosa to generate oral mucosa mesenchymal stromal cells or its secretome, was found to be a viable technique.
  • The gel created by combining these biological components with HA showed a positive impact when applied in the early stage of wound healing.

Cite This Article

APA
Di Francesco P, Cajon P, Desterke C, Perron Lepage MF, Lataillade JJ, Kadri T, Lepage OM. (2021). Effect of Allogeneic Oral Mucosa Mesenchymal Stromal Cells on Equine Wound Repair. Vet Med Int, 2021, 5024905. https://doi.org/10.1155/2021/5024905

Publication

ISSN: 2090-8113
NlmUniqueID: 101524203
Country: United States
Language: English
Volume: 2021
Pages: 5024905

Researcher Affiliations

Di Francesco, Paola
  • Unité ICE-Groupe de Recherche en Médecine et Rééducation des Equidés de Sport (GREMERES), Centre for Equine Health, Ecole Nationale Vétérinaire de Lyon, VetAgro Sup, Université de Lyon, Marcy l'Etoile 69280, France.
Cajon, Pauline
  • Stem Cell Vet Therapeutics SAS, Elancourt 78990, France.
Desterke, Christophe
  • INSERM UMR935, University of Medicine Paris Sud 11, Orsay, France.
Perron Lepage, Marie-France
  • Vet Tox Path Consulting, Theizé 69620, France.
Lataillade, Jean-Jacques
  • Institut de Recherche Biomédical des Armées, Unité de Thérapie Cellulaire et Réparation Tissulaire, Brétigny sur Orge 91223, France.
Kadri, Tewfik
  • Stem Cell Vet Therapeutics SAS, Elancourt 78990, France.
Lepage, Olivier M
  • Unité ICE-Groupe de Recherche en Médecine et Rééducation des Equidés de Sport (GREMERES), Centre for Equine Health, Ecole Nationale Vétérinaire de Lyon, VetAgro Sup, Université de Lyon, Marcy l'Etoile 69280, France.

Conflict of Interest Statement

Pauline Cajon and Tewfik Kadri are StemT\'s employees; they produced stem cell-based products but did not participate in the clinical study. The other authors declare that they have no conflicts of interest.

References

This article includes 57 references
  1. Stashak T., Theoret C. Equine Wound Management . Ames, LA, USA: Wiley- Blackwell; 2008.
  2. Theoret C. Tissue engineering in wound repair: the three “R”s repair, replace, regenerate.. Veterinary Surgery 2009;38(8):905–913.
  3. Wilmink J M, Veenman J N, van den Boom R. Differences in polymorphonucleocyte function and local inflammatory response between horses and ponies.. Equine Veterinary Journal 2003;35:561–569.
    doi: 10.2746/042516403775467234pubmed: 14515955google scholar: lookup
  4. Wilmink J M, van Weeren P R. Second-intention repair in the horse and pony and management of exuberant granulation tissue.. Veterinary Clinics of North America: Equine Practice 2005;21(1):15–32.
    doi: 10.1016/j.cveq.2004.11.014pubmed: 15691597google scholar: lookup
  5. Theoret C L, Barber S M, Moyana T N, Gordon J R. Expression of transforming growth factor beta (1), beta (3), and basic fibroblast growth factor in full-thickness skin wounds of equine limbs and thorax.. Veterinary Surgery 2005;30:269–277.
    pubmed: 11340559
  6. Schwartz A J, Wilson D A, Keegan K G. Factors regulating collagen synthesis and degradation during second-intention healing of wounds in the thoracic region and the distal aspect of the forelimb of horses.. American Journal of Veterinary Research 2002;63(11):1564–1570.
    doi: 10.2460/ajvr.2002.63.1564pubmed: 12428668google scholar: lookup
  7. Theoret C L, Wilmink J M. Aberrant wound healing in the horse: naturally occurring conditions reminiscent of those observed in man.. Wound Repair and Regeneration 2013;21(3):365–371.
    doi: 10.1111/wrr.12018pubmed: 23441750google scholar: lookup
  8. Badiavas A R, Badiavas E V. Potential benefits of allogeneic bone marrow mesenchymal stem cells for wound healing.. Expert Opinion on Biological Therapy 2011;11(11):1447–1454.
  9. Borena B M, Martens A, Broeckx S Y. Regenerative skin wound healing in mammals: state-of-the-art on growth factor and stem cell based treatments.. Cellular Physiology and Biochemistry 2015;36(1):1–23.
    doi: 10.1159/000374049pubmed: 25924569google scholar: lookup
  10. Dash N R, Dash S N, Routray P, Mohapatra S, Mohapatra P C. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells.. Rejuvenation Research 2009;12(5):359–366.
    doi: 10.1089/rej.2009.0872pubmed: 19929258google scholar: lookup
  11. Fang B, Shi M, Liao L, Yang S, Liu Y, Zhao R C. Systemic infusion of FLK1+ mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice.. Transplantation 2004;78(1):83–88.
  12. Oyagi S, Hirose M, Kojima M. Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats.. Journal of Hepatology 2006;44(4):742–748.
    doi: 10.1016/j.jhep.2005.10.026pubmed: 16469408google scholar: lookup
  13. Lange C, Tögel F, Ittrich H. Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats.. Kidney International 2005;68(4):1613–1617.
  14. Kim J W, Lee J H, Lyoo Y S, Jung D I, Park H M. The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds.. Veterinary Dermatology 2013;24(2):242–253.
    doi: 10.1111/vde.12011pmc: PMC3618380pubmed: 23432413google scholar: lookup
  15. Malhotra S, Hu M S, Marshall C D. Mesenchymal stromal cells as cell-based therapeutics for wound healing.. Stem Cells International 2016;1:2–7.
    doi: 10.1155/2016/4157934pmc: PMC4757746pubmed: 26966438google scholar: lookup
  16. Falanga V, Iwamoto S, Chartier M. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds.. Tissue Engineering 2007;13(6):1299–1312.
    doi: 10.1089/ten.2006.0278pubmed: 17518741google scholar: lookup
  17. Borena B, Pawde A, Aithal H, Kinjavdekar P, Singh R, Kumar D. Evaluation of autologous bone marrow-derived nucleated cells for healing of full-thickness skin wounds in rabbits.. International Wound Journal 2010;7(4):249–260.
  18. Wu Y, Chen L, Scott P G, Tredget E E. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis.. Stem Cells 2007;25(10):2648–2659.
    doi: 10.1634/stemcells.2007-0226pubmed: 17615264google scholar: lookup
  19. Broeckx S Y, Borena B M, Van Hecke L. Comparison of autologous versus allogeneic epithelial-like stem cell treatment in an in vivo equine skin wound model.. Cytotherapy 2015;17(10):1434–1446.
    doi: 10.1016/j.jcyt.2015.06.004pubmed: 26212608google scholar: lookup
  20. Textor J A, Clark K C, Walker N J. Allogeneic stem cells alter gene expression and improve healing of distal limb wounds in horses.. Stem Cells Translational Medicine 2018;7(1):98–108.
    doi: 10.1002/sctm.17-0071pmc: PMC5746157pubmed: 29063737google scholar: lookup
  21. Dash B C, Xu Z, Lin L. Stem cells and engineered scaffolds for regenerative wound healing.. Bioengineering 2018;5(1):p. 23.
  22. Hu L, Wang J, Zhou X. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts.. Scientific Reports 2016;6(1):p. 32993.
    doi: 10.1038/srep32993pmc: PMC5018733pubmed: 27615560google scholar: lookup
  23. Mancuso P, Raman S, Glynn A, Barry F, Murphy J M. Mesenchymal stem cell therapy for osteoarthritis: the critical role of the cell secretome.. Frontiers in Bioengineering and Biotechnology 2019;7.
    doi: 10.3389/fbioe.2019.00009pmc: PMC6361779pubmed: 30761298google scholar: lookup
  24. Wickham H. Wickham. Ggplot2 . 1st. New York, NY, USA: Springer-Verlag; 2009. Elegant graphics for data analysis; pp. 41–64.
  25. Walton G S, Neal P A. Observations on wound healing in the horse: the role of wound contraction.. Equine Veterinary Journal 1972;4(2):93–97.
  26. Jacobs K, Leach D H, Fretz P. Comparative aspect of the healing of excisional wounds on the leg and body of horses.. Veterinary Surgery 1984;13:83–90.
  27. Schnabel L V, Fortier L A, Wayne McIlwraith C, Nobert K M. Therapeutic use of stem cells in horses: which type, how, and when?. The Veterinary Journal 2013;197(3):570–577.
    doi: 10.1016/j.tvjl.2013.04.018pubmed: 23778257google scholar: lookup
  28. Maumus M, Roussignol G, Toupet K. Utility of a mouse model of osteoarthritis to demonstrate cartilage protection by ifnγ-primed equine mesenchymal stem cells.. Frontiers in Immunology 2016;7:392–410.
    doi: 10.3389/fimmu.2016.00392pmc: PMC5037129pubmed: 27729913google scholar: lookup
  29. Colbath A C, Frisbie D D, Dow S W, Kisiday J D, McIlwraith C W, Goodrich L R. Equine models for the investigation of mesenchymal stem cell therapies in orthopaedic disease.. Operative Techniques in Sports Medicine 2017;25(1):41–49.
  30. Dominici M, Le Blanc K, Mueller I. Minimal criteria for defining multipotent mesenchymal stromal cells. The international Society for Cellular Therapy position statement.. Cytotherapy 2006;8(4):315–317.
    doi: 10.1080/14653240600855905pubmed: 16923606google scholar: lookup
  31. Ding D-C, Shyu W-C, Lin S-Z. Mesenchymal stem cells.. Cell Transplantation 2011;20(1):5–14.
    doi: 10.3727/096368910xpubmed: 21396235google scholar: lookup
  32. Aguiar C, Therrien J, Lemire P, Segura M, Smith L C, Theoret C L. Differentiation of equine induced pluripotent stem cells into a keratinocyte lineage.. Equine Veterinary Journal 2016;48(3):338–345.
    doi: 10.1111/evj.12438pubmed: 25781637google scholar: lookup
  33. Sasaki M, Abe R, Fujita Y, Ando S, Inokuma D, Shimizu H. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type.. The Journal of Immunology 2008;180(4):2581–2587.
    doi: 10.4049/jimmunol.180.4.2581pubmed: 18250469google scholar: lookup
  34. Cerqueira M T, Pirraco R P, Marques A P. Stem cells in skin wound healing: are we there yet?. Advances in Wound Care 2016;5(4):164–175.
    doi: 10.1089/wound.2014.0607pmc: PMC4817598pubmed: 27076994google scholar: lookup
  35. Kidd S, Spaeth E, Dembinski J L. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging.. Stem Cells 2009;27(10):2614–2623.
    doi: 10.1002/stem.187pmc: PMC4160730pubmed: 19650040google scholar: lookup
  36. Rustad K C, Gurtner G C. Mesenchymal stem cells home to sites of injury and inflammation.. Advances in Wound Care 2012;1(4):147–152.
    doi: 10.1089/wound.2011.0314pmc: PMC3623614pubmed: 24527296google scholar: lookup
  37. Park S-R, Kim J-W, Jun H-S, Roh J Y, Lee H-Y, Hong I-S. Stem cell secretome and its effect on cellular mechanisms relevant to wound healing.. Molecular Therapy 2018;26(2):606–617.
    doi: 10.1016/j.ymthe.2017.09.023pmc: PMC5835016pubmed: 29066165google scholar: lookup
  38. Lepault E, Celeste C, Dore M, Martineau D, Theoret C L. Comparative study on microvascular occlusion and apoptosis in body and limb wounds in the horse.. Wound Repair and Regeneration 2005;13(5):520–529.
  39. Becker A D, Riet I V. Homing and migration of mesenchymal stromal cells: how to improve the efficacy of cell therapy?. World Journal of Stem Cells 2016;8(3):73–87.
    doi: 10.4252/wjsc.v8.i3.73pmc: PMC4807311pubmed: 27022438google scholar: lookup
  40. Hinderer S, Layland S L, Schenke-Layland K. ECM and ECM-like materials-biomaterials for applications in regenerative medicine and cancer therapy.. Advanced Drug Delivery Reviews 2016;97:260–269.
    doi: 10.1016/j.addr.2015.11.019pubmed: 26658243google scholar: lookup
  41. Price R D, Myers S, Leigh I M, Navsaria H A. The role of hyaluronic acid in wound healing: assessment of clinical evidence.. American Journal of Clinical Dermatology 2005;6(6):393–402.
  42. Yang G, Prestwich G D, Mann B K. Thiolated carboxymethyl-hyaluronic-acid-based biomaterials enhance wound healing in rats, dogs, and horses.. ISRN Veterinary Science 2011;2011:1–7.
    doi: 10.5402/2011/851593pmc: PMC3658841pubmed: 23738117google scholar: lookup
  43. Hadley H S, Stanley B J, Fritz M C, Hauptman J G, Steficek B A. Effects of a cross-linked hyaluronic acid based gel on the healing of open wounds in dogs.. Veterinary Surgery 2013;42(2):161–169.
  44. Patel S, Maheshwari A, Chandra A. Biomarkers for wound healing and their evaluation.. Journal of Wound Care 2016;25(1):46–55.
    doi: 10.12968/jowc.2016.25.1.46pubmed: 26762498google scholar: lookup
  45. Caputo W J, Vaquero C, Monterosa A. A retrospective study of cryopreserved umbilical cord as an adjunctive therapy to promote the healing of chronic, complex foot ulcers with underlying osteomyelitis.. Wound Repair and Regeneration 2016;24(5):885–893.
    doi: 10.1111/wrr.12456pubmed: 27312890google scholar: lookup
  46. Fortier L A, Travis A J. Stem cells in veterinary medicine.. Stem Cell Research & Therapy 2011;2(1):9–15.
    doi: 10.1186/scrt50pmc: PMC3092149pubmed: 21371354google scholar: lookup
  47. Lepage O M, Maddens S, Jorgensen C. Que pouvons-nous espérer des cellules stromales mésenchymateuses dans le traitement des affections articulaires.. Pratique Veterinaire Equine 2015;47:134–143.
  48. Mensing N, Gasse H, Hambruch N, Haeger J-D, Pfarrer C, Staszyk C. Isolation and characterization of multipotent mesenchymal stromal cells from the gingiva and the periodontal ligament of the horse.. BMC Veterinary Research 2011;7(1):p. 42.
    doi: 10.1186/1746-6148-7-42pmc: PMC3161857pubmed: 21810270google scholar: lookup
  49. Zhang Q Z, Nguyen A L, Yu W H, Le A D. Human oral mucosa and gingiva: a unique reservoir for mesenchymal stem cells.. Journal of Dental Research 2012;91(11):1011–1018.
    doi: 10.1177/0022034512461016pmc: PMC3490281pubmed: 22988012google scholar: lookup
  50. Engeland C G, Bosch J A, Cacioppo J T, Marucha P T. Mucosal wound healing: the roles of age and sex.. Archives of Surgery 2006;141(12):1193–1197.
    doi: 10.1001/archsurg.141.12.1193pubmed: 17178961google scholar: lookup
  51. Larjava H, Wiebe C, Gallant-Behm C, Hart D A, Heino J, Häkkinen L. Exploring scarless healing of oral soft tissues.. Journal (Canadian Dental Association) 2011;77:p. b18.
    pubmed: 21366956
  52. Vriens A P, Waaijman T, Van Den Hoogenband H M, De Boer E M, Scheper R J, Gibbs S. Comparison of autologous full-thickness gingiva and skin substitutes for wound healing.. Cell Transplantation 2008;17(10-11):1199–1209.
    doi: 10.3727/096368908787236521pubmed: 19181214google scholar: lookup
  53. Gibbs S, Ponec M. Intrinsic regulation of differentiation markers in human epidermis, hard palate and buccal mucosa.. Archives of Oral Biology 2000;45(2):149–158.
    doi: 10.1016/s0003-9969(99)00116-8pubmed: 10716619google scholar: lookup
  54. Boink M A, Van Den Broek L J, Roffel S. Different wound healing properties of dermis, adipose, and gingiva mesenchymal stromal cells.. Wound Repair and Regeneration 2016;24(1):100–109.
    doi: 10.1111/wrr.12380pubmed: 26542883google scholar: lookup
  55. Irwin C R, Picardo M, Ellis I. Inter- and intra-site heterogeneity in the expression of fetal-like phenotypic characteristics by gingival fibroblasts: potential significance for wound healing.. Journal of Cell Science 1994;107(5):1333–1346.
    doi: 10.1242/jcs.107.5.1333pubmed: 7929639google scholar: lookup
  56. Wilkinson H N, Hardman M J. Wound healing: cellular mechanisms and pathological outcomes.. Open Biology 2020;10(9).
    doi: 10.1098/rsob.200223pmc: PMC7536089pubmed: 32993416google scholar: lookup
  57. Zhang Q, Shi S, Liu Y. Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis.. The Journal of Immunology 2009;183(12):7787–7798.
    doi: 10.4049/jimmunol.0902318pmc: PMC2881945pubmed: 19923445google scholar: lookup

Citations

This article has been cited 4 times.
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  4. Saadh MJ, Ramírez-Coronel AA, Saini RS, Arias-Gonzáles JL, Amin AH, Gavilán JCO, Sârbu I. Advances in mesenchymal stem/stromal cell-based therapy and their extracellular vesicles for skin wound healing. Hum Cell 2023 Jul;36(4):1253-1264.
    doi: 10.1007/s13577-023-00904-8pubmed: 37067766google scholar: lookup