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RNA sequencing of mesenchymal stem cells reveals a blocking of differentiation and immunomodulatory activities under inflammatory conditions in rheumatoid arthritis patients

INTRODUCTION: Mesenchymal stem cells (MSCs) have the ability to differentiate into different types of cells of the mesenchymal lineage, such as osteocytes, chondrocytes, and adipocytes. It is also known that under inflammatory stimuli or in the appropriate experimental conditions, they can also act...

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Autores principales: Lamas, Jose Ramon, Fernandez-Gutierrez, Benjamin, Mucientes, Arkaitz, Marco, Fernando, Lopiz, Yaiza, Jover, Juan Angel, Abasolo, Lydia, Rodríguez-Rodríguez, Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501285/
https://www.ncbi.nlm.nih.gov/pubmed/31060598
http://dx.doi.org/10.1186/s13075-019-1894-y
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author Lamas, Jose Ramon
Fernandez-Gutierrez, Benjamin
Mucientes, Arkaitz
Marco, Fernando
Lopiz, Yaiza
Jover, Juan Angel
Abasolo, Lydia
Rodríguez-Rodríguez, Luis
author_facet Lamas, Jose Ramon
Fernandez-Gutierrez, Benjamin
Mucientes, Arkaitz
Marco, Fernando
Lopiz, Yaiza
Jover, Juan Angel
Abasolo, Lydia
Rodríguez-Rodríguez, Luis
author_sort Lamas, Jose Ramon
collection PubMed
description INTRODUCTION: Mesenchymal stem cells (MSCs) have the ability to differentiate into different types of cells of the mesenchymal lineage, such as osteocytes, chondrocytes, and adipocytes. It is also known that under inflammatory stimuli or in the appropriate experimental conditions, they can also act as regulators of inflammation. Thus, in addition to their regenerating potential, their interest has been extended to their possible use in cell therapy strategies for treatment of immune disorders. OBJECTIVE: To analyze, by RNA-seq analysis, the transcriptome profiling of allogenic MSCs under RA lymphocyte activation. METHODS: We identified the differentially expressed genes in bone marrow mesenchymal stem cells after exposure to an inflammatory environment. The transcriptome profiling was evaluated by means of the precise measurement of transcripts provided by the RNA-Seq technology. RESULTS: Our results evidenced the existence of blocking of both regenerative (differentiation) and immunomodulatory phenotypes under inflammatory conditions characterized by an upregulation of genes involved in immune processes and a simultaneous downregulation of genes mainly involved in regenerative or cell differentiation functions. CONCLUSIONS: We conclude that the two main functions of MSCs (immunomodulation and differentiation) are blocked, at least while the inflammation is being resolved. Inflammation, at least partially mediated by gamma-interferon, drives MSCs to a cellular distress adopting a defensive state. This knowledge could be of particular interest in cases where the damage to be repaired has an important immune-mediated component. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1894-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-65012852019-05-10 RNA sequencing of mesenchymal stem cells reveals a blocking of differentiation and immunomodulatory activities under inflammatory conditions in rheumatoid arthritis patients Lamas, Jose Ramon Fernandez-Gutierrez, Benjamin Mucientes, Arkaitz Marco, Fernando Lopiz, Yaiza Jover, Juan Angel Abasolo, Lydia Rodríguez-Rodríguez, Luis Arthritis Res Ther Research Article INTRODUCTION: Mesenchymal stem cells (MSCs) have the ability to differentiate into different types of cells of the mesenchymal lineage, such as osteocytes, chondrocytes, and adipocytes. It is also known that under inflammatory stimuli or in the appropriate experimental conditions, they can also act as regulators of inflammation. Thus, in addition to their regenerating potential, their interest has been extended to their possible use in cell therapy strategies for treatment of immune disorders. OBJECTIVE: To analyze, by RNA-seq analysis, the transcriptome profiling of allogenic MSCs under RA lymphocyte activation. METHODS: We identified the differentially expressed genes in bone marrow mesenchymal stem cells after exposure to an inflammatory environment. The transcriptome profiling was evaluated by means of the precise measurement of transcripts provided by the RNA-Seq technology. RESULTS: Our results evidenced the existence of blocking of both regenerative (differentiation) and immunomodulatory phenotypes under inflammatory conditions characterized by an upregulation of genes involved in immune processes and a simultaneous downregulation of genes mainly involved in regenerative or cell differentiation functions. CONCLUSIONS: We conclude that the two main functions of MSCs (immunomodulation and differentiation) are blocked, at least while the inflammation is being resolved. Inflammation, at least partially mediated by gamma-interferon, drives MSCs to a cellular distress adopting a defensive state. This knowledge could be of particular interest in cases where the damage to be repaired has an important immune-mediated component. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1894-y) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-06 2019 /pmc/articles/PMC6501285/ /pubmed/31060598 http://dx.doi.org/10.1186/s13075-019-1894-y 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 Research Article
Lamas, Jose Ramon
Fernandez-Gutierrez, Benjamin
Mucientes, Arkaitz
Marco, Fernando
Lopiz, Yaiza
Jover, Juan Angel
Abasolo, Lydia
Rodríguez-Rodríguez, Luis
RNA sequencing of mesenchymal stem cells reveals a blocking of differentiation and immunomodulatory activities under inflammatory conditions in rheumatoid arthritis patients
title RNA sequencing of mesenchymal stem cells reveals a blocking of differentiation and immunomodulatory activities under inflammatory conditions in rheumatoid arthritis patients
title_full RNA sequencing of mesenchymal stem cells reveals a blocking of differentiation and immunomodulatory activities under inflammatory conditions in rheumatoid arthritis patients
title_fullStr RNA sequencing of mesenchymal stem cells reveals a blocking of differentiation and immunomodulatory activities under inflammatory conditions in rheumatoid arthritis patients
title_full_unstemmed RNA sequencing of mesenchymal stem cells reveals a blocking of differentiation and immunomodulatory activities under inflammatory conditions in rheumatoid arthritis patients
title_short RNA sequencing of mesenchymal stem cells reveals a blocking of differentiation and immunomodulatory activities under inflammatory conditions in rheumatoid arthritis patients
title_sort rna sequencing of mesenchymal stem cells reveals a blocking of differentiation and immunomodulatory activities under inflammatory conditions in rheumatoid arthritis patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501285/
https://www.ncbi.nlm.nih.gov/pubmed/31060598
http://dx.doi.org/10.1186/s13075-019-1894-y
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