Immune response to allogeneic equine mesenchymal stromal cells

Area of Science:

• Immunology
• Cell Biology
• Veterinary Medicine

Background:

• Mesenchymal stromal cells (MSCs) are considered hypoimmunogenic, suggesting potential for allogeneic transplantation.
• Equine bone marrow-derived MSCs were utilized to investigate their immunomodulatory properties.

Purpose of the Study:

• To evaluate the immunogenicity of equine MSCs from different breeds and MHC II expression levels.
• To determine the suitability of MSCs for allogeneic administration in horses.

Main Methods:

• MSCs were isolated from Connemara, Standardbred, and Thoroughbred horses.
• MSCs were categorized by MHC II expression and screened for universal blood donor characteristics.
• Co-culture assays with responder leukocytes, complement treatments, and equine leukocyte antigen (ELA) haplotyping were performed.

Main Results:

• Allogeneic MSCs were ELA mismatched with responder leukocytes.
• MHC II-low and universal blood donor MSCs did not induce peripheral blood mononuclear cell proliferation or CD8 lymphocyte activation.
• Universal blood donor MSCs increased T regulatory cells, while MHC II-high MSCs showed transient neutrophil activation.

Conclusions:

• MHC II-low MSCs are optimal for allogeneic use, preventing innate and adaptive immune activation.
• These MSCs exhibit increased metabolic and gene expression compared to other allogeneic MSC types.