MHC compatibility influences the interaction between different types of equine mesenchymal stem/stromal cells and the local immune response.
Abstract: The allogeneic administration of equine mesenchymal stem/stromal cells (MSCs) has numerous advantages over autologous therapy, but their interactions with the patient's immune system need to be further elucidated. These interactions can be influenced by factors such as the compatibility between donor-receptor for the major histocompatibility complex (MHC) and by the MHC expression levels, which can change under different conditions like inflammatory exposure and chondrogeneic differentiation. In this study, we evaluated the local immune response induced by chondrogeneically differentiated (MSC-chondro), pro-inflammatory primed (MSC-primed) and basal (MSC-naïve) MSCs, and how this response changes the immunomodulatory and immunogenic profiles of MSCs in vivo. Equine MSCs were embedded in alginate scaffolds and subcutaneously implanted into autologous, MHC-matched and MHC-mismatched horses. Scaffolds were recovered at different time-points for histologic and gene expression analyses, and the procedure was repeated to assess the effect of a second administration. Our results suggest that MHC-compatibility may play a key role in attenuating the local immune response induced by MSCs, which may be related to the upregulation of immunomodulatory genes in the three MSC types in vivo. In contrast, when MSCs were administered into MHC-mismatched horses, expression of immunogenic genes was higher across all MSC conditions. Therefore, the conditions in which MSCs are administered may not affect the long-term local immune response, but MHC-matched administration would favour the immune evasion of MSCs, thus being advisable especially when repeated MSC administrations are required. Comprehensively investigating the in vivo immune response against equine allogeneic MSCs is crucial for advancing veterinary cell therapies.
Copyright © 2025. Published by Elsevier Ltd.
Publication Date: 2025-09-03 PubMed ID: 40915193DOI: 10.1016/j.rvsc.2025.105889Google Scholar: Lookup
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- Journal Article
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APA
Cequier A, Serrano MB, Soler-Monsó MT, Bernad E, Vázquez FJ, Vitoria A, Fuente S, Zaragoza P, Romero A, Rodellar C, Barrachina L.
(2025).
MHC compatibility influences the interaction between different types of equine mesenchymal stem/stromal cells and the local immune response.
Res Vet Sci, 196, 105889.
https://doi.org/10.1016/j.rvsc.2025.105889 Publication
Researcher Affiliations
- Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, Zaragoza, Spain.
- Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain.
- Departament de Patologia, Hospital Universitari Bellvitge, Unitat multidisciplinar de càncer de mama, Institut de Investigació Biomèdica de Bellvitge (IDIBELL), Institut Català d'Oncologia (ICO), Barcelona, Spain.
- Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain.
- Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, Zaragoza, Spain.
- Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, Zaragoza, Spain.
- Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, Zaragoza, Spain.
- Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain.
- Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, Zaragoza, Spain.
- Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain.
- Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, Zaragoza, Spain. Electronic address: lbarrach@unizar.es.
MeSH Terms
- Animals
- Horses / immunology
- Mesenchymal Stem Cells / immunology
- Major Histocompatibility Complex / immunology
- Mesenchymal Stem Cell Transplantation / veterinary
- Tissue Scaffolds
Conflict of Interest Statement
Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose.
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