Therapeutic Potential in Wound Healing of Allogeneic Use of Equine Umbilical Cord Mesenchymal Stem Cells

Author:

Iribarne Ailén1,Palma María Belén12ORCID,Andrini Laura1ORCID,Riccillo Fernando1,Rodriguez Delfina3,Casella Martín4,Garay Felipe45,Zabala Julieta Spoto45,Mazza Leandro6,Muro Adriana7,Buero Guillermo8,Miriuka Santiago G.2,Carosella Edgardo910,García Marcela N.1

Affiliation:

1. Cátedra de Citología, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Buenos Aires CP 1900, Argentina

2. Instituto de Neurociencias (INEU), Fundación para la Lucha contra Enfermedades Neurológicas de la Infancia-Consejo Nacional de Investigaciones Científicas y Técnicas (FLENI-CONICET) Escobar, Buenos Aires CP B1625, Argentina

3. Centro de Reproducción Equina La Adela, Chascomús, Buenos Aires CP 7130, Argentina

4. División Remonta Haras La Teruca, Buenos Aires B1900, Argentina

5. Dirección Veterinaria, Policía de la Provincia de Buenos Aires, Buenos Aires B1904, Argentina

6. Cátedra de Anatomía B, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Buenos Aires CP 1900, Argentina

7. Laboratorio de Análisis Clínicos Veterinarios, La Plata, Buenos Aires CP 1900, Argentina

8. Sanatorio Mater Dei, Ciudad Autónoma de Buenos Aires, Buenos Aires CP C1425, Argentina

9. Commissariat a l’Energie Atomique et aux Energies Alternatives (CEA), Service de Recherche en Hemato-Immunologie (SRHI), Saint-Louis Hospital, 75010 Paris, France

10. Hopital Saint-Louis, IUH, Université Paris Diderot, Sorbonne Paris Cite, 75010 Paris, France

Abstract

Wound healing after skin injury is a complex process, particularly in equines where leg wounds are prevalent and their repair is complicated due to the anatomical characteristics. Conventional treatments are not effective enough. The umbilical cord offers an unlimited source of adult mesenchymal stem cells (ucMSCs) from Wharton’s jelly tissue. The present study aims to demonstrate the safety and therapeutic potential of the allogeneic use of equine ucMSCs (e-ucMSCs) in the healing of severe equine leg wounds. The methods employed were the isolation, culture and expansion of e-ucMSCs. Flow cytometry and a PCR assay were used for cell characterization. This study included an immunomodulation assay, a murine pre-clinical trial and the first phase of an equine clinical trial. Our results showed that e-ucMSCs express a functional HLA-G homolog, EQMHCB2. In the immunomodulation assay, the e-ucMSCs inhibited the proliferation of activated equine peripheral blood mononuclear cells (e-PBMCs). In the murine pre-clinical trial, e-ucMSCs reduced healing time by 50%. In the equine clinical trial, the injection of e-ucMSCs into severe leg lesions improved the closure time and quality of the tissues involved, regenerating them without fibrous tissue scar formation. In conclusion, the results of this study suggest that e-ucMSCs can be used allogeneically for wound healing by creating a tolerogenic environment.

Funder

MINCyT (Ministerio de Ciencia y Tecnología) of Argentina

Publisher

MDPI AG

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