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Serum-Mediated Oxidative Stress from Systemic Sclerosis Patients Affects Mesenchymal Stem Cell Function
OBJECTIVES: Properties of mesenchymal stromal/stem cells (MSCs) from systemic sclerosis (SSc) patients have been reported to be altered. MSC-based therapy may therefore rely on the use of allogeneic MSCs from healthy subjects. Here, we investigated whether heterologous MSCs could exhibit altered pro...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585199/ https://www.ncbi.nlm.nih.gov/pubmed/28919892 http://dx.doi.org/10.3389/fimmu.2017.00988 |
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author | Fonteneau, Guillaume Bony, Claire Goulabchand, Radjiv Maria, Alexandre T. J. Le Quellec, Alain Rivière, Sophie Jorgensen, Christian Guilpain, Philippe Noël, Danièle |
author_facet | Fonteneau, Guillaume Bony, Claire Goulabchand, Radjiv Maria, Alexandre T. J. Le Quellec, Alain Rivière, Sophie Jorgensen, Christian Guilpain, Philippe Noël, Danièle |
author_sort | Fonteneau, Guillaume |
collection | PubMed |
description | OBJECTIVES: Properties of mesenchymal stromal/stem cells (MSCs) from systemic sclerosis (SSc) patients have been reported to be altered. MSC-based therapy may therefore rely on the use of allogeneic MSCs from healthy subjects. Here, we investigated whether heterologous MSCs could exhibit altered properties following exposure to oxidative environment of SSc sera. METHODS: Human bone marrow-derived MSCs were cultured in the presence of various sera: control human serum AB (SAB), SAB with HOCl-induced AOPPs at 400 or 1,000 µmol/L (SAB(400) or SAB(1000), respectively), or H(2)O(2)-induced AOPPs or SSc patient serum (PS). Proliferation, apoptosis, and senescence rates of MSCs were evaluated after 3, 6, and 10 days in culture. Reactive oxygen species and nitric oxide production were quantified at 24 h. Trilineage potential of differentiation was tested after 21 days in specific culture conditions and immunosuppressive function measured in a T lymphocyte proliferative assay. RESULTS: In the presence of oxidative environment of PS, MSCs retained their proliferative potential and survived for at least the first 3 days of exposure, while the number of senescent MSCs increased at day 6 and apoptosis rate at day 10. Exposure to PS enhanced the antioxidant capacity of MSCs, notably the expression of SOD2 antioxidant gene. By contrast, the osteoblastic/adipogenic potential of MSCs was increased, whereas their immunosuppressive function was slightly reduced. DISCUSSION: Although some functional properties of MSCs were affected upon culture with PS, evidence from preclinical studies and the present one suggested that MSCs can adapt to the oxidative environment and exert their therapeutic effect. |
format | Online Article Text |
id | pubmed-5585199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-55851992017-09-15 Serum-Mediated Oxidative Stress from Systemic Sclerosis Patients Affects Mesenchymal Stem Cell Function Fonteneau, Guillaume Bony, Claire Goulabchand, Radjiv Maria, Alexandre T. J. Le Quellec, Alain Rivière, Sophie Jorgensen, Christian Guilpain, Philippe Noël, Danièle Front Immunol Immunology OBJECTIVES: Properties of mesenchymal stromal/stem cells (MSCs) from systemic sclerosis (SSc) patients have been reported to be altered. MSC-based therapy may therefore rely on the use of allogeneic MSCs from healthy subjects. Here, we investigated whether heterologous MSCs could exhibit altered properties following exposure to oxidative environment of SSc sera. METHODS: Human bone marrow-derived MSCs were cultured in the presence of various sera: control human serum AB (SAB), SAB with HOCl-induced AOPPs at 400 or 1,000 µmol/L (SAB(400) or SAB(1000), respectively), or H(2)O(2)-induced AOPPs or SSc patient serum (PS). Proliferation, apoptosis, and senescence rates of MSCs were evaluated after 3, 6, and 10 days in culture. Reactive oxygen species and nitric oxide production were quantified at 24 h. Trilineage potential of differentiation was tested after 21 days in specific culture conditions and immunosuppressive function measured in a T lymphocyte proliferative assay. RESULTS: In the presence of oxidative environment of PS, MSCs retained their proliferative potential and survived for at least the first 3 days of exposure, while the number of senescent MSCs increased at day 6 and apoptosis rate at day 10. Exposure to PS enhanced the antioxidant capacity of MSCs, notably the expression of SOD2 antioxidant gene. By contrast, the osteoblastic/adipogenic potential of MSCs was increased, whereas their immunosuppressive function was slightly reduced. DISCUSSION: Although some functional properties of MSCs were affected upon culture with PS, evidence from preclinical studies and the present one suggested that MSCs can adapt to the oxidative environment and exert their therapeutic effect. Frontiers Media S.A. 2017-09-01 /pmc/articles/PMC5585199/ /pubmed/28919892 http://dx.doi.org/10.3389/fimmu.2017.00988 Text en Copyright © 2017 Fonteneau, Bony, Goulabchand, Maria, Le Quellec, Rivière, Jorgensen, Guilpain and Noël. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Fonteneau, Guillaume Bony, Claire Goulabchand, Radjiv Maria, Alexandre T. J. Le Quellec, Alain Rivière, Sophie Jorgensen, Christian Guilpain, Philippe Noël, Danièle Serum-Mediated Oxidative Stress from Systemic Sclerosis Patients Affects Mesenchymal Stem Cell Function |
title | Serum-Mediated Oxidative Stress from Systemic Sclerosis Patients Affects Mesenchymal Stem Cell Function |
title_full | Serum-Mediated Oxidative Stress from Systemic Sclerosis Patients Affects Mesenchymal Stem Cell Function |
title_fullStr | Serum-Mediated Oxidative Stress from Systemic Sclerosis Patients Affects Mesenchymal Stem Cell Function |
title_full_unstemmed | Serum-Mediated Oxidative Stress from Systemic Sclerosis Patients Affects Mesenchymal Stem Cell Function |
title_short | Serum-Mediated Oxidative Stress from Systemic Sclerosis Patients Affects Mesenchymal Stem Cell Function |
title_sort | serum-mediated oxidative stress from systemic sclerosis patients affects mesenchymal stem cell function |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585199/ https://www.ncbi.nlm.nih.gov/pubmed/28919892 http://dx.doi.org/10.3389/fimmu.2017.00988 |
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