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Summary   Background  Allogeneic mesenchymal stem cells ( MSC s) are a promising cell source for treating musculoskeletal injuries in horses. Controversy exists, however, over whether major histocompatibility complex ( MHC )‐mismatched  MSC s are recognised by the recipient immune system and targeted for death by a cytotoxic antibody response.    Objectives  To determine if cytotoxic anti‐ MHC  antibodies generated in vivo following  MHC ‐mismatched  MSC  injections are capable of initiating complement‐dependent cytotoxicity of  MSC s.    Study design  Experimental controlled study.    Methods  Antisera previously collected at Days 0, 7, 14 and 21 post‐injection from 4 horses injected with donor  MHC ‐mismatched equine leucocyte antigen ( ELA )‐A2 haplotype  MSC s and one control horse injected with donor  MHC ‐matched  ELA ‐A2  MSC s were utilised in this study. Antisera were incubated with  ELA ‐A2  MSC s before adding complement in microcytotoxicity assays and cell death was analysed via eosin dye exclusion.  ELA ‐A2 peripheral blood leucocytes ( PBL s) were used in the assays as a positive control.    Results  Antisera from all 4 horses injected with  MHC ‐mismatched  MSC s contained antibodies that caused the death of  ELA ‐A2 haplotype  MSC s in the microcytotoxicity assays. In 2 of the 4 horses, antibodies were present as early as Day 7 post‐injection.  MSC  death was consistently equivalent to that of  ELA ‐A2 haplotype  PBL  death at all time points and antisera dilutions. Antisera from the control horse that was injected with  MHC ‐matched  MSC s did not contain cytotoxic  ELA ‐A2 antibodies at any of the time points examined.    Main limitations  This study examined MSC death in vitro only and utilized antisera from a small number of horses.    Conclusions  The cytotoxic antibody response induced in recipient horses following injection with donor  MHC ‐mismatched  MSC s is capable of killing donor  MSC s in vitro. These results suggest that the use of allogeneic  MHC ‐mismatched  MSC s must be cautioned against, not only for potential adverse events, but also for reduced therapeutic efficacy due to targeted  MSC  death.

equine veterinary journal

Allogeneic major histocompatibility complex‐mismatched equine bone marrow‐derived mesenchymal stem cells are targeted for death by cytotoxic anti‐major histocompatibility complex antibodies