337
Views
10
CrossRef citations to date
0
Altmetric
Original Article

Articular and subcutaneous adipose tissues of rheumatoid arthritis patients represent equal sources of immunoregulatory mesenchymal stem cells

, , , , , & show all
Pages 441-450 | Received 04 May 2017, Accepted 25 Nov 2017, Published online: 06 Dec 2017
 

Abstract

Adipose-derived mesenchymal stem cells (ASCs) have immunoregulatory properties, but their activity is dependent on signals provided by the local microenvironment. It is likely that highly inflammatory milieu of rheumatoid joint affects ASCs activity. To test this hypothesis, the function of rheumatoid ASCs derived from articular adipose tissue (AT-ASCs) and ASCs derived from subcutaneous adipose tissue (Sc-ASCs) has been analysed. Articular adipose tissue (infrapatellar fat pad) and subcutaneous adipose tissue (from the site of skin closure with sutures) were obtained from rheumatoid arthritis (RA) patients undergoing total knee joint replacement surgery. ASCs were isolated accordingly to the routinely applied procedure, expanded and treated or not with IFNγ and TNF (10 ng/ml). To evaluate immunomodulatory properties of AT- and Sc-ASCs, co-cultures with peripheral blood mononuclear cells (PBMCs) from healthy donors have been set. Proliferation of activated PBMCs (3H-thymidine incorporation method), secretion of IL-10 and IL-17A in co-culture supernatants (specific ELISA tests) and T regulatory FoxP3+ cells (Tregs) percentage have been evaluated (flow cytometry). Performed experiments demonstrated that ASCs from both sources have comparable properties. They suppress proliferation of activated PBMCs to the similar extent, induce IL-10 secretion by resting PBMCs and moderately induce generation of FoxP3+ Treg cells. Interestingly, both AT-ASCs and Sc-ASCs cause increase of IL-17A secretion by activated PBMCs as well as induce up-regulation of IL-6 concentration in co-culture supernatants. We demonstrated that AT-ASCs and Sc-ASCs obtained from RA patients possess similar immunomodulatory properties despite different localization and distinct cytokine milieu of tissue of origin. Our results indicate that ASCs derived from rheumatoid adipose tissues are not strongly immunosuppressive in vitro and that they may contribute to the pathogenesis of RA due to IL-17A secretion enhancement.

Acknowledgements

We thank professor Paweł Małdyk from the Rheumoortopaedic Clinic of the Institute of Rheumatology in Warsaw and his patients for providing adipose tissue for this study.

Disclosure statement

The authors declare no conflict of interest. All authors are employed in the National Institute of Geriatrics, Rheumatology and Rehabilitation (NIGRiR) in Warsaw, Poland.

Additional information

Funding

This work was supported by the National Science Centre in Poland (Grant No. 2015/17/D/NZ5/02219) and by the NIGRiR Statutory Grant (Grant No. S/33).

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access
  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 65.00 Add to cart
* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.