Allorecognition of Mesenchymal Stem Cells is Dependent on Major Histocompatibility Complex Haplotype

Introduction: Long considered nonimmunogenic and immunomodulatory, allo-MSCs are used and often preferred for their reduced cost, off-the-shelf availability, better-characterized cell quality, and ease of FDA approval of cell lines as compared with autologous preparations. Subsequently, there are numerous veterinary reports on clinical use of allogeneic MSCs. In contrast, we have previously shown allorecognition causes an increased adverse response to repeated allogeneic MSC administration in the horse. Our current objective was to determine if allorecognition is due to MHC mismatch.

Materials and Methods: We performed repeated intra-articular injections (day 0 and day 29) with either MHC matched (n = 12) or MHC mismatched (n = 12) allogeneic MSCs and autologous MSCs (n = 6) and measured postinjection clinical response and antibody development.

Results: There was no significant difference in lameness, but significantly more edema in horses injected with mismatch MSCs on day 30 compared with autologous or matched MSCs. There was significantly greater antibody development in horses injected with mismatch MSCs on days 28 to 63 that resulted in cytotoxicity of MSCs.

Discussion/Conclusion: This is further evidence that immune mediated recognition occurs after allo-MSC administration and is likely to negatively affect efficacy.

Acknowledgment: Funding by Linda and Dennis H. Clark '68 Chair in Equine Studies and Link Endowment for Equine Research.