Analyze Diet
Animals : an open access journal from MDPI2024; 14(13); doi: 10.3390/ani14131842

Equine Corneal Wound Healing Using Mesenchymal Stem Cell Secretome: Case Report.

Abstract: Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative approach, the ASC secretome, a rich source of trophic factors, cytokines, and extracellular vesicles, was topically administered to the affected eye. Remarkably, within one week of secretome treatment, the clinical signs of blepharospasm and epiphora resolved, and the corneal ulcer exhibited complete re-epithelialization, regained transparency, and reduced neovascularization. No recurrence was observed during the 1.5-year follow-up period. This case highlights the potential therapeutic benefits of the ASC secretome in promoting corneal wound healing and suggests its promise as a novel cell-free therapy for treating refractory corneal ulcers in horses.
Publication Date: 2024-06-21 PubMed ID: 38997954PubMed Central: PMC11240377DOI: 10.3390/ani14131842Google 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.
  • Case Reports
  • 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 research presents a case where a previously untreatable corneal ulcer in a horse was successfully treated with a substance produced by mesenchymal stem cells from adipose tissue, which showed promising implications for improving corneal wound healing in horses.

Objective of the Research

  • The main goal of this study was to evaluate the efficacy of using the secretome from adipose tissue-derived mesenchymal stem cells (ASCs) to treat corneal ulcers in horses which have proved resistant to conventional treatments.

Research Methodology

  • The mare was initially treated with traditional therapies involving antibiotics, anti-inflammatory drugs, and surgical debridement but showed no signs of healing, having persistent epithelial defects and stromal complications.
  • As an alternative therapy, the researchers opted to use the ASC secretome, administered topically to the afflicted area of the eye. The secretome is a combination of growth factors, cytokines, and extracellular vesicles, products of the ASCs.

Findings and Conclusion

  • In a span of one week after initiating the treatment with the ASC secretome, the horse recuperated significantly, with visible signs of corneal re-epithelialization, regain of transparency, decrease in neovascularization, and resolution of clinical signs such as blepharospasm and epiphora.
  • No recurrence of the ulcer was encountered during the follow-up period of 1.5 years, indicating the effectiveness and potential benefits of the ASC secretome in fostering corneal wound healing.
  • The positive outcome from this case study points out the potential of ASC secretome as a novel, non-cellular therapy for the treatment of stubborn corneal ulcers in horses. This method may present promising implications for veterinary medicine and equine health care in the future.

Cite This Article

APA
Casado-Santos A, González-Cubero E, González-Fernández ML, González-Rodríguez Y, García-Rodríguez MB, Villar-Suárez V. (2024). Equine Corneal Wound Healing Using Mesenchymal Stem Cell Secretome: Case Report. Animals (Basel), 14(13). https://doi.org/10.3390/ani14131842

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 14
Issue: 13

Researcher Affiliations

Casado-Santos, Alejandro
  • Department of Surgery, Medicine and Veterinary Anatomy, Faculty of Veterinary Sciences, Campus de Vegazana, University of Léon, 24071 Léon, Spain.
González-Cubero, Elsa
  • Department of Neurosurgery, Stanford School of Medicine, Stanford University, Palo Alto, CA 94305, USA.
González-Fernández, Maria Luisa
  • Department of Surgery, Medicine and Veterinary Anatomy, Faculty of Veterinary Sciences, Campus de Vegazana, University of Léon, 24071 Léon, Spain.
González-Rodríguez, Yaiza
  • Department of Surgery, Medicine and Veterinary Anatomy, Faculty of Veterinary Sciences, Campus de Vegazana, University of Léon, 24071 Léon, Spain.
García-Rodríguez, Mª Belén
  • Department of Surgery, Medicine and Veterinary Anatomy, Faculty of Veterinary Sciences, Campus de Vegazana, University of Léon, 24071 Léon, Spain.
Villar-Suárez, Vega
  • Department of Surgery, Medicine and Veterinary Anatomy, Faculty of Veterinary Sciences, Campus de Vegazana, University of Léon, 24071 Léon, Spain.
  • Institute of Biomedicine (IBIOMED), Faculty of Veterinary Sciences, Campus de Vegazana, University of León, 24071 León, Spain.

Conflict of Interest Statement

The authors declare no conflicts of interest.

References

This article includes 29 references
  1. Hartley C. Differential Diagnosis and Management of Corneal Ulceration in Horses, Part 2. In Practice 2015;37:23–30.
    doi: 10.1136/inp.g6815google scholar: lookup
  2. Michau TM, Schwabenton B, Davidson MG, Gilger BC. Superficial, Nonhealing Corneal Ulcers in Horses: 23 Cases (1989–2003). Vet. Ophthalmol. 2003;6:291–297.
  3. Prucha VJS, Tichy A, Nell B. Equine Non-Healing Corneal Ulcers: A Retrospective Evaluation of 57 Cases (2001–2017). Tierarztl. Prax. Ausg. G Grosstiere. Nutztiere. 2020;48:92–97.
    doi: 10.1055/a-1124-2953pubmed: 32325498google scholar: lookup
  4. Williams LB, Pinard CL. Corneal Ulcers in Horses. Compend. Contin. Educ. Vet. 2013;35:E4.
    pubmed: 23532729
  5. Cooley PL, Wyman M. Indolent-like Corneal Ulcers in 3 Horses. J. Am. Vet. Med. Assoc. 1986;188:295–297.
    pubmed: 3949604
  6. Hempstead JE, Clode AB, Borst LB, Gilger BC. Histopathological Features of Equine Superficial, Nonhealing, Corneal Ulcers. Vet. Ophthalmol. 2014;17((Suppl. S1)):46–52.
    doi: 10.1111/vop.12117pubmed: 25126664google scholar: lookup
  7. Mohan RR, Kempuraj D, D’Souza S, Ghosh A. Corneal Stromal Repair and Regeneration. Prog. Retin. Eye Res. 2022;91:101090.
  8. Morgan RV, Abrams KL. A Comparison of Six Different Therapies for Persistent Corneal Erosions in Dogs and Cats. Vet. Comp. Ophthalmol. 1994;4:38–43.
  9. Falcão MSA, Brunel HDSS, Peixer MAS, Dallago BSL, Costa FF, Queiroz LM, Campbell P, Malard PF. Effect of Allogeneic Mesenchymal Stem Cells (MSCs) on Corneal Wound Healing in Dogs. J. Tradit. Complement. Med. 2020;10:440–445.
    doi: 10.1016/j.jtcme.2019.04.006pmc: PMC7484966pubmed: 32953559google scholar: lookup
  10. Gugjoo M.B. Therapeutic Applications of Mesenchymal Stem Cells in Veterinary Medicine. Springer Nature; Singapore: 2022. Mesenchymal Stem Cells Therapeutic Applications in Eye and Adnexa Ailments; pp. 391–408.
  11. Singh VK, Sharma P, Vaksh UKS, Chandra R. Current Approaches for the Regeneration and Reconstruction of Ocular Surface in Dry Eye. Front. Med. 2022;9:885780.
    doi: 10.3389/fmed.2022.885780pmc: PMC9544815pubmed: 36213677google scholar: lookup
  12. Alió del Barrio JL, De la Mata A, De Miguel MP, Arnalich-Montiel F, Nieto-Miguel T, El Zarif M, Cadenas-Martín M, López-Paniagua M, Galindo S, Calonge M. Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells. Cells 2022;11:2549.
    doi: 10.3390/cells11162549pmc: PMC9406486pubmed: 36010626google scholar: lookup
  13. Xia J, Minamino S, Kuwabara K, Arai S. Stem Cell Secretome as a New Booster for Regenerative Medicine. Biosci. Trends. 2019;13:299–307.
    doi: 10.5582/BST.2019.01226pubmed: 31527327google scholar: lookup
  14. Makridakis M, Roubelakis MG, Vlahou A. Stem Cells: Insights into the Secretome. Biochim. Biophys. Acta. 2013;1834:2380–2384.
    doi: 10.1016/j.bbapap.2013.01.032pubmed: 23376432google scholar: lookup
  15. 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
  16. Keshtkar S, Azarpira N, Ghahremani MH. Mesenchymal Stem Cell-Derived Extracellular Vesicles: Novel Frontiers in Regenerative Medicine. Stem Cell Res. Ther. 2018;9:63.
    doi: 10.1186/s13287-018-0791-7pmc: PMC5845209pubmed: 29523213google scholar: lookup
  17. Pawitan JA. Prospect of Stem Cell Conditioned Medium in Regenerative Medicine. Biomed Res. Int. 2014;2014:965849.
    doi: 10.1155/2014/965849pmc: PMC4229962pubmed: 25530971google scholar: lookup
  18. Bellei B, Migliano E, Tedesco M, Caputo S, Papaccio F, Lopez G, Picardo M. Adipose Tissue-Derived Extracellular Fraction Characterization: Biological and Clinical Considerations in Regenerative Medicine. Stem Cell Res. Ther. 2018;9:207.
    doi: 10.1186/s13287-018-0956-4pmc: PMC6085647pubmed: 30092820google scholar: lookup
  19. Peyrecave-Capo X, Saulnier N, Maddens S, Gremillet B, Desjardins I. Equine Umbilical Cord Serum Composition and Its Healing Effects in Equine Corneal Ulceration. Front. Vet. Sci. 2022;9:843744.
    doi: 10.3389/fvets.2022.843744pmc: PMC8970184pubmed: 35372560google scholar: lookup
  20. Gama KB, Santos DS, Evangelista AF, Silva DN, de Alcântara AC, Dos Santos RR, Soares MBP, Villarreal CF. Conditioned Medium of Bone Marrow-Derived Mesenchymal Stromal Cells as a Therapeutic Approach to Neuropathic Pain: A Preclinical Evaluation. Stem Cells Int. 2018;2018:8179013.
    doi: 10.1155/2018/8179013pmc: PMC5831939pubmed: 29535781google scholar: lookup
  21. Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine. Int. J. Mol. Sci. 2017;18:1852.
    doi: 10.3390/ijms18091852pmc: PMC5618501pubmed: 28841158google scholar: lookup
  22. An S, Anwar K, Ashraf M, Lee H, Jung R, Koganti R, Ghassemi M, Djalilian AR. Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of Exosomes. Pharmaceutics 2023;15:1486.
  23. Saccu G, Menchise V, Gai C, Bertolin M, Ferrari S, Giordano C, Manco M, Dastrù W, Tolosano E, Bussolati B. Bone Marrow Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles Promote Corneal Wound Repair by Regulating Inflammation and Angiogenesis. Cells 2022;11:3892.
    doi: 10.3390/cells11233892pmc: PMC9736484pubmed: 36497151google scholar: lookup
  24. Fernandes-Cunha GM, Na KS, Putra I, Lee HJ, Hull S, Cheng YC, Blanco IJ, Eslani M, Djalilian AR, Myung D. Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier. Stem Cells Transl. Med. 2019;8:478–489.
    doi: 10.1002/sctm.18-0178pmc: PMC6477005pubmed: 30644653google scholar: lookup
  25. El-Husseiny HM, Mady EA, Helal MAY, Tanaka R. The Pivotal Role of Stem Cells in Veterinary Regenerative Medicine and Tissue Engineering. Vet. Sci. 2022;9:648.
    doi: 10.3390/vetsci9110648pmc: PMC9698002pubmed: 36423096google scholar: lookup
  26. Mendt M, Rezvani K, Shpall E. Mesenchymal Stem Cell-Derived Exosomes for Clinical Use. Bone Marrow Transplant. 2019;54:789–792.
    doi: 10.1038/s41409-019-0616-zpubmed: 31431712google scholar: lookup
  27. Meissner JM, Chmielińska A, Ofri R, Cisło-Sankowska A, Marycz K. Extracellular Vesicles Isolated from Equine Adipose-Derived Stromal Stem Cells (ASCs) Mitigate Tunicamycin-Induced ER Stress in Equine Corneal Stromal Stem Cells (CSSCs). Curr. Issues Mol. Biol. 2024;46:3251–3277.
    doi: 10.3390/cimb46040204pmc: PMC11048834pubmed: 38666934google scholar: lookup
  28. Harrell CR, 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
  29. Freitas NPP, Silva BDP, Bezerra MRL, Pescini LYG, Olinda RG, Salgueiro CCDM, Nunes JF, Martins JAM, Neto SG, Martins LT. Freeze-Dried Platelet-Rich Plasma and Stem Cell-Conditioned Medium for Therapeutic Use in Horses. J. Equine Vet. Sci. 2023;121:104189.
    doi: 10.1016/j.jevs.2022.104189pubmed: 36464033google scholar: lookup