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PReS-FINAL-2107: In vitro investigation into mesenchymal stromal cells as a potential therapeutic in juvenile arthritis
© Wienke et al.; licensee BioMed Central Ltd. 2013
Published: 5 December 2013
Mesenchymal stromal cells (MSC) are multipotent cells with an immune suppressive capacity. In the last decade the therapeutic application of these cells has been tested in inflammatory diseases like graft versus host disease and rheumatoid arthritis. Injection of MSC can be a potential therapy for juvenile idiopathic arthritis patients refractory to conventional therapies.
We tested the mechanisms of MSC immune modulation with a specific focus on the suppression of synovial fluid derived immune cells.
We setup an in vitro culture system to test the suppressive capacity of MSC on both peripheral blood cells (PBMC) and synovial fluid cells (SFMC). We tested T cell proliferation and cytokine production of healthy controls and JIA patients. Furthermore, we investigated the induction or suppression of regulatory T cells (Treg) and Th17 cells as these cells have an important role in JIA pathogenesis and tested the effect of inflammatory cytokines and monocytes on MSC suppression.
MSC dose dependently suppressed both PBMC and SFMC, but SF T cells were less receptive towards MSC suppression. Tnfa and ifng were suppressed in both PBMC and SFMC, but IL-17 was not affected. In PBMC, but not SFMC, Th17 cell numbers were reduced by MSC and Treg numbers increased. We found no clear role for monocytes or inflammatory cytokines tnfa and ifng in activating the immune suppressive activity of MSC as published before.
We conclude that MSC can suppress T cells derived from JIA synovial fluid. However, this suppression is reduced as compared to T cells derived from peripheral blood.
Disclosure of interest
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.