Mouse bone marrow-derived mesenchymal stem cells acquire immunogenicity concurrent with differentiation to insulin-producing cells

Abstract Background Although mesenchymal stem cells (MSCs) are regarded as immune-elusive and even immunosuppressive, recent evidence suggests that allogeneic immune response might is inevitable in the case of some lineages differentiated from MSCs. Regarding the importance of allogeneic IPCs and MSCs in pre-clinical and clinical studies, the present study aimed to investigate the possible changes in the immunogenicity of MSCs during the differentiation to IPCs in a murine model of allogeneic transplantation. Material and methods Two mouse strains, C57BL/6 (H2Db) and BALB/c (H2Dd) were selected to establish an allogeneic cell transplantation model. Bone marrow MSCs were differentiated into IPCs and the expression of H2D, CD80, and Qa-2 molecules were evaluated via flowcytometry on MSCs and IPCs. The differentiated and undifferentiated MSCs were encountered to allogeneic splenocytes and the proliferation, CD44 activation marker, and cytokine release in the splenocytes were evaluated. Results IPCs exhibited increased expression of MHC-I and CD80 that elicited an allogenic response including the activation-induced proliferation of splenocytes, activation of CD4+ T cells, and IFNγ response. Conclusions MSCs acquire immunogenicity after differentiation to functional IPCs, which might cause decreased efficacy in the case of allogeneic transplantation. Careful precautions might be critical for saving the IPCs against the detrimental allogeneic responses.