system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, METHODS, RESULTS. Meshes: Animals, Antibodies, Antibody Formation, Bone Marrow, Bone Marrow Cells, Horses, Major Histocompatibility Complex, Mesenchymal Stem Cells.
user
Are allogeneic MHC-mismatched equine bone marrow-derived mesenchymal stem cells targeted for death by cytotoxic anti-MHC antibodies? Context: Allogeneic mesenchymal stem cells (MSCs) are a promising cell source for treating musculoskeletal injuries in horses. Controversy exists, however, over whether major histocompatibility complex (MHC)-mismatched MSCs are recognised by the recipient immune system and targeted for death by a cytotoxic antibody response. To determine if cytotoxic anti-MHC antibodies generated in-vivo following MHC-mismatched MSC injections are capable of initiating complement-dependent cytotoxicity of MSCs. Experimental controlled study. Antisera previously collected at days 0, 7, 14, and 21 post-injection from four horses injected with donor MHC-mismatched Equine Leukocyte Antigen (ELA)-A2 haplotype MSCs and one control horse injected with donor MHC-matched ELA-A2 MSCs were utilised in this study. Antisera were incubated with ELA-A2 MSCs before adding complement in microcytoxicity assays and cell death was analysed via eosin dye exclusion. ELA-A2 peripheral blood leukocytes (PBLs) were used in the assays as a positive control. Antisera from all four horses injected with MHC-mismatched MSCs contained antibodies that caused the death of ELA-A2 haplotype MSCs in the microcytotoxicity assays. In two of the four 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 MSCs did not contain cytotoxic ELA-A2 antibodies at any of the time points examined.
assistant
The cytotoxic antibody response induced in recipient horses following injection with donor MHC-mismatched MSCs is capable of killing donor MSCs in-vitro. These results suggest that the use of allogeneic MHC-mismatched MSCs must be cautioned against, not only for potential adverse events, but also for reduced therapeutic efficacy due to targeted MSC death. This article is protected by copyright. All rights reserved. Final Decision: yes