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vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis
BACKGROUND: Recent efforts in osteoarthritis (OA) research have highlighted synovial inflammation and involvement of immune cells in disease onset and progression. We sought to establish the in-vivo immune response in collagenase-induced OA and investigate the ability of human mesenchymal stem cells...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870800/ https://www.ncbi.nlm.nih.gov/pubmed/27194025 http://dx.doi.org/10.1186/s13287-016-0331-2 |
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author | Farrell, Eric Fahy, Niamh Ryan, Aideen E Flatharta, Cathal O O’Flynn, Lisa Ritter, Thomas Murphy, J Mary |
author_facet | Farrell, Eric Fahy, Niamh Ryan, Aideen E Flatharta, Cathal O O’Flynn, Lisa Ritter, Thomas Murphy, J Mary |
author_sort | Farrell, Eric |
collection | PubMed |
description | BACKGROUND: Recent efforts in osteoarthritis (OA) research have highlighted synovial inflammation and involvement of immune cells in disease onset and progression. We sought to establish the in-vivo immune response in collagenase-induced OA and investigate the ability of human mesenchymal stem cells (hMSCs) overexpressing viral interleukin 10 (vIL-10) to modulate immune populations and delay/prevent disease progression. METHODS: Eight-week-old male C57BL/6 mice were injected with 1 U type VII collagenase over two consecutive days. At day 7, 20,000 hMSCs overexpressing vIL-10 were injected into the affected knee. Control groups comprised of vehicle, 20,000 untransduced or adNull-transduced MSCs or virus alone. Six weeks later knees were harvested for histological analysis and popliteal and inguinal lymph nodes for flow cytometric analysis. RESULTS: At this time there was no significant difference in knee OA scores between any of the groups. A trend toward more damage in animals treated with hMSCs was observed. Interestingly there was a significant reduction in the amount of activated CD4 and CD8 T cells in the vIL-10-expressing hMSC group. CONCLUSIONS: vIL-10-overexpressing hMSCs can induce long-term reduction in activated T cells in draining lymph nodes of mice with collagenase-induced OA. This could lead to reduced OA severity or disease progression over the long term. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-016-0331-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4870800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-48708002016-05-19 vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis Farrell, Eric Fahy, Niamh Ryan, Aideen E Flatharta, Cathal O O’Flynn, Lisa Ritter, Thomas Murphy, J Mary Stem Cell Res Ther Research BACKGROUND: Recent efforts in osteoarthritis (OA) research have highlighted synovial inflammation and involvement of immune cells in disease onset and progression. We sought to establish the in-vivo immune response in collagenase-induced OA and investigate the ability of human mesenchymal stem cells (hMSCs) overexpressing viral interleukin 10 (vIL-10) to modulate immune populations and delay/prevent disease progression. METHODS: Eight-week-old male C57BL/6 mice were injected with 1 U type VII collagenase over two consecutive days. At day 7, 20,000 hMSCs overexpressing vIL-10 were injected into the affected knee. Control groups comprised of vehicle, 20,000 untransduced or adNull-transduced MSCs or virus alone. Six weeks later knees were harvested for histological analysis and popliteal and inguinal lymph nodes for flow cytometric analysis. RESULTS: At this time there was no significant difference in knee OA scores between any of the groups. A trend toward more damage in animals treated with hMSCs was observed. Interestingly there was a significant reduction in the amount of activated CD4 and CD8 T cells in the vIL-10-expressing hMSC group. CONCLUSIONS: vIL-10-overexpressing hMSCs can induce long-term reduction in activated T cells in draining lymph nodes of mice with collagenase-induced OA. This could lead to reduced OA severity or disease progression over the long term. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-016-0331-2) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-18 /pmc/articles/PMC4870800/ /pubmed/27194025 http://dx.doi.org/10.1186/s13287-016-0331-2 Text en © Farrell et al. 2016 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 | Research Farrell, Eric Fahy, Niamh Ryan, Aideen E Flatharta, Cathal O O’Flynn, Lisa Ritter, Thomas Murphy, J Mary vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis |
title | vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis |
title_full | vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis |
title_fullStr | vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis |
title_full_unstemmed | vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis |
title_short | vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis |
title_sort | vil-10-overexpressing human mscs modulate naïve and activated t lymphocytes following induction of collagenase-induced osteoarthritis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870800/ https://www.ncbi.nlm.nih.gov/pubmed/27194025 http://dx.doi.org/10.1186/s13287-016-0331-2 |
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