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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...

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Autores principales: Farrell, Eric, Fahy, Niamh, Ryan, Aideen E, Flatharta, Cathal O, O’Flynn, Lisa, Ritter, Thomas, Murphy, J Mary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
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.
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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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