Authors: Cequier Alina, Vázquez Francisco José, Vitoria Arantza, Bernad Elvira, Fuente Sara, Serrano María Belén, Zaragoza María Pilar, Romero Antonio, Rodellar Clementina, Barrachina Laura
Journal: Frontiers in veterinary science
Summary
# Editorial Summary: Immunogenicity of Allogeneic Equine Mesenchymal Stem Cells The clinical success of allogeneic mesenchymal stem cell (MSC) therapy in horses depends critically on minimising adverse immune responses whilst harnessing beneficial immunomodulatory effects, yet the factors influencing these responses remain incompletely understood. Cequier and colleagues investigated how donor-recipient major histocompatibility complex (MHC) matching and MSC conditioning—specifically pro-inflammatory priming or chondrogenic differentiation—shaped systemic immune recognition in horses receiving repeated subcutaneous MSC administrations, measuring T cell proliferation, regulatory T cell (Treg) activation, B cell responses, and interferon gamma secretion. MHC-mismatched recipients consistently mounted stronger helper and cytotoxic T lymphocyte responses and elevated interferon gamma production across all MSC types; however, the magnitude of response varied substantially according to MSC conditioning, with pro-inflammatory primed MSCs triggering the most robust initial response but paradoxically activating Treg populations and showing stable responses to repeat administration. Conversely, naïve and chondrogenically differentiated MSCs induced weaker immediate responses but promoted sustained B lymphocyte activation and amplified cellular responses following second administration—suggesting potential for cumulative sensitisation. For practitioners employing allogeneic MSCs therapeutically, these findings indicate that MHC-matched donors warrant particular emphasis for primed or repeatedly administered naïve cell protocols, whilst chondrogenically differentiated MSCs may offer greater flexibility regarding MHC compatibility, though B cell sensitisation requires monitoring in long-term treatment schedules.
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Practical Takeaways
- •If using allogeneic MSC therapy in horses, prioritize MHC-matched donors for naive or primed cell products to minimize recipient immune rejection
- •Pre-treating MSCs through chondrogenic differentiation may reduce acute immune responses, making it useful for MHC-mismatched applications, though B cell responses still warrant monitoring
- •For repeated MSC administrations, primed cells show stable immune tolerance while naive cells demonstrate escalating immune responses—treatment planning should account for single vs. repeated dosing protocols
Key Findings
- •MHC-mismatched allogeneic MSCs induced significantly higher helper and cytotoxic T lymphocyte proliferation and IFN-γ secretion compared to MHC-matched MSCs
- •Pro-inflammatory primed MSCs (MSC-primed) generated the strongest immune response but activated regulatory T cells and showed consistent response between first and second administration
- •Chondrogenically differentiated MSCs (MSC-chondro) induced lower overall immune response with greater B cell activation and proportionally higher cellular response after repeated administration
- •MHC-matched donor selection is particularly critical for primed and naive MSCs, while MHC-matching is less critical for chondrogenically differentiated MSCs