CELLEQUS: an MHC haplo-bank of equine mesenchymal stem cells (MSCs) from homozygous donors

Allogeneic cell therapy presents advantages over autologous therapy, but immune recognition of foreign cells can compromise safety and effectiveness. In equine mesenchymal stem cells (MSCs), such recognition is related to the matching or mismatching for the major histocompatibility complex (MHC) between donor and recipient, and to the immune profile of MSCs.

To improve allogeneic MSC treatments in horses, our goal was to create CELLEQUS: a bank of equine MSCs derived from homozygous donors for the most frequent MHChaplotypes, focusing on the most common breeds in Spain. This bank will facilitate the use of MHC-matched MSCs with a well-characterized immune profile.

First, we used a panel of 10 intra-MHC microsatellites (Sadeghi et al., 2018) to study MHC diversity in Purebred Spanish, Purebred Arabian, Hispano-Arabian and Lusitano horses, and determine the most common MHC-haplotypes. Second, we searched homozygous horses for the most frequent MHChaplotypes and recruited them as bone marrow MSC donors. Third, MSCs (n=9) underwent characterization through immunophenotyping (CD90, CD105, CD44, CD45, CD11, MHC-I, MHC-II; flow cytometry) and gene expression (MHC-I, MHC-II, IL6, COX2; RT-qPCR).

Importantly, donors with the same haplotype can exhibit very different immune profiles, so not all homozygous horses would be equally suitable as donors. So far, no correlation has been observed between the MHC-haplotype and the expression levels (gene or surface) of MHC-I and MHC-II. CELLEQUS Bank arises from applying knowledge on the equine genome to improve equine health, by providing critical foundational resources for the advancement of veterinary regenerative medicine, spanning research and clinical application.

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