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Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions?
BACKGROUND: Bone marrow mesenchymal stem cells (BM-MSCs) can dampen inflammation in animal models of inflammatory rheumatisms and human osteoarthritis. They are expected to be a solution for numerous human conditions. However, in rheumatoid arthritis (RA) and spondyloarthritis (SpA), subsets of subc...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854713/ https://www.ncbi.nlm.nih.gov/pubmed/31722720 http://dx.doi.org/10.1186/s13075-019-2014-8 |
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author | Berthelot, Jean-Marie Le Goff, Benoit Maugars, Yves |
author_facet | Berthelot, Jean-Marie Le Goff, Benoit Maugars, Yves |
author_sort | Berthelot, Jean-Marie |
collection | PubMed |
description | BACKGROUND: Bone marrow mesenchymal stem cells (BM-MSCs) can dampen inflammation in animal models of inflammatory rheumatisms and human osteoarthritis. They are expected to be a solution for numerous human conditions. However, in rheumatoid arthritis (RA) and spondyloarthritis (SpA), subsets of subchondral BM-MSCs might conversely fuel synovitis and enthesitis. MAIN TEXT: Abnormal behaviour of BM-MSCs and/or their progeny has been found in RA and SpA. BM-MSCs also contribute to the ossifying processes observed in ankylosing spondylitis. Some synovial fibroblastic stem cells probably derive from BM-MSCs, but some stem cells can also migrate through the bare zone area of joints, not covered by cartilage, into the synovium. BM-MSCs can also migrate in the synovium over tendons. Sub-populations of bone marrow stem cells also invade the soft tissue side of enthesis via small holes in the bone cortex. The present review aims (1) to make a focus on these two aspects and (2) to put forward the hypothesis that lasting epigenetic changes of some BM-MSCs, induced by transient infections of the bone marrow close to the synovium and/or entheses (i.e. trained immunity of BM-MSCs and/or their progeny), contribute to the pathogenesis of inflammatory rheumatisms. Such hypothesis would fit with (1) the uneven distribution and/or flares of arthritis and enthesitis observed at the individual level in RA and SpA (reminiscent of what is observed following reactive arthritis and/or in Whipple’s disease); (2) the subchondral bone marrow oedema and erosions occurring in many RA patients, in the bare zone area; and (3) the frequent relapses of RA and SpA despite bone marrow transplantation, whereas most BM-MSCs resist graft preconditioning. CONCLUSION: Some BM-MSCs might be more the problem than the solution in inflammatory rheumatisms. Subchondral bone marrow BM-MSCs and their progeny trafficking through the bare zone area of joints or holes in the bone cortex of entheses should be thoroughly studied in RA and SpA respectively. This may be done first in animal models. Mini-arthroscopy of joints could also be used in humans to specifically sample tissues close to the bare zone and/or enthesis areas. |
format | Online Article Text |
id | pubmed-6854713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68547132019-11-21 Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions? Berthelot, Jean-Marie Le Goff, Benoit Maugars, Yves Arthritis Res Ther Review BACKGROUND: Bone marrow mesenchymal stem cells (BM-MSCs) can dampen inflammation in animal models of inflammatory rheumatisms and human osteoarthritis. They are expected to be a solution for numerous human conditions. However, in rheumatoid arthritis (RA) and spondyloarthritis (SpA), subsets of subchondral BM-MSCs might conversely fuel synovitis and enthesitis. MAIN TEXT: Abnormal behaviour of BM-MSCs and/or their progeny has been found in RA and SpA. BM-MSCs also contribute to the ossifying processes observed in ankylosing spondylitis. Some synovial fibroblastic stem cells probably derive from BM-MSCs, but some stem cells can also migrate through the bare zone area of joints, not covered by cartilage, into the synovium. BM-MSCs can also migrate in the synovium over tendons. Sub-populations of bone marrow stem cells also invade the soft tissue side of enthesis via small holes in the bone cortex. The present review aims (1) to make a focus on these two aspects and (2) to put forward the hypothesis that lasting epigenetic changes of some BM-MSCs, induced by transient infections of the bone marrow close to the synovium and/or entheses (i.e. trained immunity of BM-MSCs and/or their progeny), contribute to the pathogenesis of inflammatory rheumatisms. Such hypothesis would fit with (1) the uneven distribution and/or flares of arthritis and enthesitis observed at the individual level in RA and SpA (reminiscent of what is observed following reactive arthritis and/or in Whipple’s disease); (2) the subchondral bone marrow oedema and erosions occurring in many RA patients, in the bare zone area; and (3) the frequent relapses of RA and SpA despite bone marrow transplantation, whereas most BM-MSCs resist graft preconditioning. CONCLUSION: Some BM-MSCs might be more the problem than the solution in inflammatory rheumatisms. Subchondral bone marrow BM-MSCs and their progeny trafficking through the bare zone area of joints or holes in the bone cortex of entheses should be thoroughly studied in RA and SpA respectively. This may be done first in animal models. Mini-arthroscopy of joints could also be used in humans to specifically sample tissues close to the bare zone and/or enthesis areas. BioMed Central 2019-11-13 2019 /pmc/articles/PMC6854713/ /pubmed/31722720 http://dx.doi.org/10.1186/s13075-019-2014-8 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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. |
spellingShingle | Review Berthelot, Jean-Marie Le Goff, Benoit Maugars, Yves Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions? |
title | Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions? |
title_full | Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions? |
title_fullStr | Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions? |
title_full_unstemmed | Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions? |
title_short | Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions? |
title_sort | bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854713/ https://www.ncbi.nlm.nih.gov/pubmed/31722720 http://dx.doi.org/10.1186/s13075-019-2014-8 |
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