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Allogeneic major histocompatibility complex‐mismatched equine bone marrow‐derived mesenchymal stem cells are targeted for death by cytotoxic anti‐major histocompatibility complex antibodies
Author(s) -
Berglund A.K.,
Schnabel L.V.
Publication year - 2017
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.1111/evj.12647
Subject(s) - cytotoxic t cell , major histocompatibility complex , immunology , antiserum , antibody , complement dependent cytotoxicity , antigen , biology , medicine , monoclonal antibody , in vitro , antibody dependent cell mediated cytotoxicity , genetics
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.