Impaired alloreactivity of chondro- and osteogenic differentiated adipose tissue-derived stem cells

Mesenchymal stem cells lack or express low levels of major histocompatibility complex (MHC) class II and other immunoactive co-stimulatory molecules rendering them “immunoincompetency”. We have shown that human adipose tissue-derived stem cells (hASCs) implanted subcutaneously in micedid 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 4h, 10h and 24h. 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-α and surface markers (CD206++, CD336++, MHC II+ and CD86++) detection. These data suggest the potential of hASCs in a xenogenic tissue engineering and regenerative medicine approachs for research routine procedures, as well as for host immune system modulation in autoimmune diseases.

Acknowledgments: TCS and RPP acknowledge RL3-TECT-NORTE-01-0124-FEDER-000020, co-financed by ON.2-O Novo Norte and European Research Council grant agreement ERC-2012-ADG 20120216-321266 for project ComplexiTE; MTC acknowledges FCT grant SFRH/BPD/96611/2013. 

1-Santos, TC et al., Tissue Eng A, 19(7-8): 83, 2013.