Adipose Tissue-derived Stem Cells do not Elicit Alloreactivity after Chondrogenic and Osteogenic Differentiation

Mesenchymal stem cells lack or express low levels of major histocompatibility complex (MHC) class II and other immunoactive costimulatory molecules rendering them ‘‘immunoincompetent’’. We have shown that human adipose tissue-derived stem cells (hASCs) implanted subcutaneously in mice did not elicit adverse immune responses 1. In this study we hypothesised that undifferentiated hASCs, and derived osteoblasts and chondrocytes, are able to evade xenogeneic immune system by failing activating murine bone marrow-derived macrophages (mBMMØs) and dendritic cells (DCs). Murine BMMØs or DCs were plated in direct contact with undifferentiated and osteo- or chondro-differentiated hASCs for 4 h, 10 h and 24 h. The cytokine profile was evaluated by qRT-PCR and the surface markers detected by flow cytometry. The direct interaction of both cell types was observed by time lapse microscopy. Results showed that mBMMØs and DCs did not depict an activated profile after contacting tissue culture polystyrene. This profile was maintained along the experiment in direct contact with undifferentiated, osteo- or chondro-differentiated hASCs. This was confirmed by the expression of IL-1, IL-4, IL-10 and TNF-a and ORAL ABSTRACTS S-43 surface markers (CD206 + + , CD336 + + , MHC II+ and CD86 + + ) detection. These data suggest the potential of hASCs in a xenogenic tissue engineering and regenerative medicine approach for research routine procedures, as well as for host immune system modulation in autoimmune diseases.