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Identifying Biomarkers of Wharton’s Jelly Mesenchymal Stromal Cells Using a Dynamic Metabolic Model: The Cell Passage Effect

Because of their unique ability to modulate the immune system, mesenchymal stromal cells (MSCs) are widely studied to develop cell therapies for detrimental immune and inflammatory disorders. However, controlling the final cell phenotype and determining immunosuppressive function following cell ampl...

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Autores principales: Laflaquière, Benoît, Leclercq, Gabrielle, Choey, Chandarong, Chen, Jingkui, Peres, Sabine, Ito, Caryn, Jolicoeur, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876007/
https://www.ncbi.nlm.nih.gov/pubmed/29495309
http://dx.doi.org/10.3390/metabo8010018
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author Laflaquière, Benoît
Leclercq, Gabrielle
Choey, Chandarong
Chen, Jingkui
Peres, Sabine
Ito, Caryn
Jolicoeur, Mario
author_facet Laflaquière, Benoît
Leclercq, Gabrielle
Choey, Chandarong
Chen, Jingkui
Peres, Sabine
Ito, Caryn
Jolicoeur, Mario
author_sort Laflaquière, Benoît
collection PubMed
description Because of their unique ability to modulate the immune system, mesenchymal stromal cells (MSCs) are widely studied to develop cell therapies for detrimental immune and inflammatory disorders. However, controlling the final cell phenotype and determining immunosuppressive function following cell amplification in vitro often requires prolonged cell culture assays, all of which contribute to major bottlenecks, limiting the clinical emergence of cell therapies. For instance, the multipotent Wharton’s Jelly mesenchymal stem/stromal cells (WJMSC), extracted from human umbilical cord, exhibit immunosuppressive traits under pro-inflammatory conditions, in the presence of interferon-γ (IFNγ), and tumor necrosis factor-α (TNFα). However, WJMSCs require co-culture bioassays with immune cells, which can take days, to confirm their immunomodulatory function. Therefore, the establishment of robust cell therapies would benefit from fast and reliable characterization assays. To this end, we have explored the metabolic behaviour of WJMSCs in in vitro culture, to identify biomarkers that are specific to the cell passage effect and the loss of their immunosuppressive phenotype. We clearly show distinct metabolic behaviours comparing WJMSCs at the fourth (P4) and the late ninth (P9) passages, although both P4 and P9 cells do not exhibit significant differences in their low immunosuppressive capacity. Metabolomics data were analysed using an in silico modelling platform specifically adapted to WJMSCs. Of interest, P4 cells exhibit a glycolytic metabolism compared to late passage (P9) cells, which show a phosphorylation oxidative metabolism, while P4 cells show a doubling time of 29 h representing almost half of that for P9 cells (46 h). We also clearly show that fourth passage WJMSCs still express known immunosuppressive biomarkers, although, this behaviour shows overlapping with a senescence phenotype.
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spelling pubmed-58760072018-03-30 Identifying Biomarkers of Wharton’s Jelly Mesenchymal Stromal Cells Using a Dynamic Metabolic Model: The Cell Passage Effect Laflaquière, Benoît Leclercq, Gabrielle Choey, Chandarong Chen, Jingkui Peres, Sabine Ito, Caryn Jolicoeur, Mario Metabolites Article Because of their unique ability to modulate the immune system, mesenchymal stromal cells (MSCs) are widely studied to develop cell therapies for detrimental immune and inflammatory disorders. However, controlling the final cell phenotype and determining immunosuppressive function following cell amplification in vitro often requires prolonged cell culture assays, all of which contribute to major bottlenecks, limiting the clinical emergence of cell therapies. For instance, the multipotent Wharton’s Jelly mesenchymal stem/stromal cells (WJMSC), extracted from human umbilical cord, exhibit immunosuppressive traits under pro-inflammatory conditions, in the presence of interferon-γ (IFNγ), and tumor necrosis factor-α (TNFα). However, WJMSCs require co-culture bioassays with immune cells, which can take days, to confirm their immunomodulatory function. Therefore, the establishment of robust cell therapies would benefit from fast and reliable characterization assays. To this end, we have explored the metabolic behaviour of WJMSCs in in vitro culture, to identify biomarkers that are specific to the cell passage effect and the loss of their immunosuppressive phenotype. We clearly show distinct metabolic behaviours comparing WJMSCs at the fourth (P4) and the late ninth (P9) passages, although both P4 and P9 cells do not exhibit significant differences in their low immunosuppressive capacity. Metabolomics data were analysed using an in silico modelling platform specifically adapted to WJMSCs. Of interest, P4 cells exhibit a glycolytic metabolism compared to late passage (P9) cells, which show a phosphorylation oxidative metabolism, while P4 cells show a doubling time of 29 h representing almost half of that for P9 cells (46 h). We also clearly show that fourth passage WJMSCs still express known immunosuppressive biomarkers, although, this behaviour shows overlapping with a senescence phenotype. MDPI 2018-02-24 /pmc/articles/PMC5876007/ /pubmed/29495309 http://dx.doi.org/10.3390/metabo8010018 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Laflaquière, Benoît
Leclercq, Gabrielle
Choey, Chandarong
Chen, Jingkui
Peres, Sabine
Ito, Caryn
Jolicoeur, Mario
Identifying Biomarkers of Wharton’s Jelly Mesenchymal Stromal Cells Using a Dynamic Metabolic Model: The Cell Passage Effect
title Identifying Biomarkers of Wharton’s Jelly Mesenchymal Stromal Cells Using a Dynamic Metabolic Model: The Cell Passage Effect
title_full Identifying Biomarkers of Wharton’s Jelly Mesenchymal Stromal Cells Using a Dynamic Metabolic Model: The Cell Passage Effect
title_fullStr Identifying Biomarkers of Wharton’s Jelly Mesenchymal Stromal Cells Using a Dynamic Metabolic Model: The Cell Passage Effect
title_full_unstemmed Identifying Biomarkers of Wharton’s Jelly Mesenchymal Stromal Cells Using a Dynamic Metabolic Model: The Cell Passage Effect
title_short Identifying Biomarkers of Wharton’s Jelly Mesenchymal Stromal Cells Using a Dynamic Metabolic Model: The Cell Passage Effect
title_sort identifying biomarkers of wharton’s jelly mesenchymal stromal cells using a dynamic metabolic model: the cell passage effect
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876007/
https://www.ncbi.nlm.nih.gov/pubmed/29495309
http://dx.doi.org/10.3390/metabo8010018
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