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Metabolites 2018, 8(1), 18; https://doi.org/10.3390/metabo8010018

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

1
Department of Chemical Engineering, Research Laboratory in Applied Metabolic Engineering, École Polytechnique de Montréal, C.P.6079, Centre-ville Station, Montréal, QC H3C 3A7, Canada
2
Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, 501 Smyth Rd. CCW 5105a, Ottawa, ON K1H 8L6, Canada
3
LRI, Université Paris-Sud, CNRS, Université Paris-Saclay, 91405 Orsay, France
4
MaIAGE, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France
*
Author to whom correspondence should be addressed.
Received: 22 December 2017 / Revised: 8 February 2018 / Accepted: 22 February 2018 / Published: 24 February 2018
(This article belongs to the Special Issue Metabolomics Modelling)
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Abstract

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. View Full-Text
Keywords: metabolomics; Wharton’s Jelly mesenchymal stem/stromal cells (WJMSC); immunosuppression; biomarkers metabolomics; Wharton’s Jelly mesenchymal stem/stromal cells (WJMSC); immunosuppression; biomarkers
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Laflaquière, B.; Leclercq, G.; Choey, C.; Chen, J.; Peres, S.; Ito, C.; Jolicoeur, M. Identifying Biomarkers of Wharton’s Jelly Mesenchymal Stromal Cells Using a Dynamic Metabolic Model: The Cell Passage Effect. Metabolites 2018, 8, 18.

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