Background Adipose-derived mesenchymal stem cells (ASCs) have immunomodulatory properties, but their activity is dependent on signals provided by local microenvironment. It is likely that proinflammatory milieu of rheumatoid joint affects ASCs activity. To test this hypothesis, the function of rheumatoid ASCs derived from articular adipose tissue (AT-ASC) and ASCs derived from subcutaneous adipose tissue (Sc-ASCs) have been analysed.
Materials and methods Articular adipose tissue (infrapatellar fat pad) and subcutaneous adipose tissue (from the site of skin closure with sutures) were obtained from 8 RA patients undergoing total knee joint replacement surgery. Then, ASCs were isolated accordingly to routinely applied procedure. ASCs were treated or not with IFNγ and TNF. To evaluate immunomodulatory properties of AT- and Sc-ASCs, co-cultures with peripheral blood mononuclear cells (PBMCs) from healthy donors have been set and then, select parameters of PBMCs function have been measured. Proliferation of activated PBMCs (flow cytometry and 3H-thymidine incorporation method), secretion of IL-10 and IL-17A in co-culture supernatants (ELISA tests) and T regulatory FoxP3+ cells (Tregs) percentage have been evaluated (flow cytometry).
Results AT- and Sc-ASCs activity in vitro is comparable. Unstimulated AT- and Sc-ASCs inhibit PBMCs proliferation and induce IL-10 secretion but increase also IL-17A production by PBMCs. In the majority of cases, ASCs presence causes increase of Tregs number. Under IFNγ and TNF stimulation ASCs exert stronger antiproliferative potential toward activated PBMCs than unstimulated ASCs, but decrease IL-10 secretion in co-cultures. Importantly, interindividual differences in the level of immunosuppressiveness of ASCs from different patients occur, especially relating to their antiproliferative potential.
Conclusions Our study demonstrates that immunosuppressive function of ASCs derived from two different sources, that is infrapatellar fat pad and subcutaneous adipose tissue, are comparable. Subcutaneous adipose tissue is isolated from the site of sutures – the localization close to the inflamed joint. Thus, it seems that conditions in the two adipose tissue sources are not very distinct which results in similar activity of AT- and Sc-ASCs.
Acknowledgements This work was supported by the Polish National Science Centre grant no. 2015/17/D/NZ5/02219 and by the statutory grant of National Institute of Geriatrics, Rheumatology and Rehabilitation no. S/33.
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