Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis

We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining o...

Full description

Bibliographic Details
Main Authors: Kay, Alasdair G., Long, Grace, Tyler, George, Stefan, Andrei, Broadfoot, Stephen J., Piccinini, Anna M., Middleton, Jim, Kehoe, Oksana
Format: Article
Published: Nature Publishing Group 2017
Online Access:https://eprints.nottingham.ac.uk/49015/
_version_ 1848797903070429184
author Kay, Alasdair G.
Long, Grace
Tyler, George
Stefan, Andrei
Broadfoot, Stephen J.
Piccinini, Anna M.
Middleton, Jim
Kehoe, Oksana
author_facet Kay, Alasdair G.
Long, Grace
Tyler, George
Stefan, Andrei
Broadfoot, Stephen J.
Piccinini, Anna M.
Middleton, Jim
Kehoe, Oksana
author_sort Kay, Alasdair G.
building Nottingham Research Data Repository
collection Online Access
description We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis.
first_indexed 2025-11-14T20:11:16Z
format Article
id nottingham-49015
institution University of Nottingham Malaysia Campus
institution_category Local University
last_indexed 2025-11-14T20:11:16Z
publishDate 2017
publisher Nature Publishing Group
recordtype eprints
repository_type Digital Repository
spelling nottingham-490152020-05-04T19:23:49Z https://eprints.nottingham.ac.uk/49015/ Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis Kay, Alasdair G. Long, Grace Tyler, George Stefan, Andrei Broadfoot, Stephen J. Piccinini, Anna M. Middleton, Jim Kehoe, Oksana We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis. Nature Publishing Group 2017-12-21 Article PeerReviewed Kay, Alasdair G., Long, Grace, Tyler, George, Stefan, Andrei, Broadfoot, Stephen J., Piccinini, Anna M., Middleton, Jim and Kehoe, Oksana (2017) Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis. Scientific Reports, 7 . p. 18019. ISSN 2045-2322 https://www.nature.com/articles/s41598-017-18144-w doi:10.1038/s41598-017-18144-w doi:10.1038/s41598-017-18144-w
spellingShingle Kay, Alasdair G.
Long, Grace
Tyler, George
Stefan, Andrei
Broadfoot, Stephen J.
Piccinini, Anna M.
Middleton, Jim
Kehoe, Oksana
Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis
title Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis
title_full Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis
title_fullStr Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis
title_full_unstemmed Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis
title_short Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis
title_sort mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis
url https://eprints.nottingham.ac.uk/49015/
https://eprints.nottingham.ac.uk/49015/
https://eprints.nottingham.ac.uk/49015/