Chondrogenic Differentiation Alters the Immunosuppressive Property of Bone Marrow-Derived Mesenchymal Stem Cells, and the Effect Is Partially due to the Upregulated Expression of B7 Molecules

Abstract

Abstract To investigate the immunosuppressive properties of MSCs, in the present study we examined the immunogenicity of undifferentiated and trilineage-differentiated (chondrocytes, osteoblasts, and adipocytes) rat bone marrow-derived MSCs under xenogeneic conditions. After chondrogenic differentiation, rat bone marrow-derived MSCs stimulated human dendritic cells (hDCs) derived from peripheral blood monocytes, leading to eight- and fourfold higher lymphocyte proliferation and cytotoxicity than that of undifferentiated MSCs. The chondrogenic-differentiated MSCs were chemotactic to hDCs in Dunn chamber chemotaxis system and were rosetted by hDCs in rosette assays. Flow cytometry analysis revealed that chondrogenic-differentiated MSCs had promoted hDC maturation, causing higher CD83 expression in hDCs, whereas undifferentiated MSCs and osteogenic- and adipogenic-differentiated MSCs showed an inhibitory effect on hDC maturation. The costimulatory B7 molecules were upregulated only in the chondrogenic-differentiated MSCs. After blocking B7 molecules with specific monoclonal antibodies in the chondrogenic-differentiated MSCs, CD83 expression of cocultured hDCs was greatly reduced. In conclusion, chondrogenic differentiation may increase the immunogenicity of MSCs, leading to stimulation of dendritic cells. The upregulated expression of B7 molecules on the chondrogenic-differentiated MSCs may be partially responsible for this event.