The immunogenicity of allogeneic mesenchymal stem cells (MSC) and their differentiated progeny in vivo under regular or inflammatory conditions will be addressed using established mouse models of allorecognition and spontaneous autoimmune diabetes. Survival and homing of MSC in vivo in syngeneic and allogeneic recipients will be investigated by tracking MSC. Allorecognition of mouse MSC in vivo will be assessed using CD8+ T cells from BM3 T cell receptor transgenic mice, which specifically recognise the MHC class I molecule H2Kb. The importance of antigen presenting cells (APC) and helper T cells in allorecognition of allogeneic MSC in vivo will also be examined. The non obese diabetic (NOD) mouse model will allow investigation of the immunogenicity of MSC in vivo in an inflammatory environment. The effect of IFN-gamma activation of MSC prior to in vivo transplantation into NOD mice will determine the role of this cytokine in the development of a hypo-immunogenic phenotype of MSC in vivo. The reparative and immunosuppressive ability of MSC, activated MSC and insulin producing islet-like differentiated MSC in autoimmune diabetes in vivo will be assessed using the NOD mouse.
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