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Identifying biomarkers of Wharton's Jelly mesenchymal stromal cells using a dynamic metabolic model: the cell passage effect

Benoît Laflaquière, Gabrielle Leclercq, Chandarong Choey, Jingkui Chen, Sabine Peres, Caryn Ito, Mario Jolicoeur

Article (2018)

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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-gamma (IFNgamma), and tumor necrosis factor-alpha (TNFalpha). 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.

Uncontrolled Keywords

Wharton's Jelly mesenchymal stem/stromal cells (WJMSC); biomarkers; immunosuppression; metabolomics

Subjects: 1800 Chemical engineering > 1800 Chemical engineering
5100 Cell biology > 5100 Cell biology
5100 Cell biology > 5106 Extracellular matrix
Department: Department of Chemical Engineering
Research Center: Other
PolyPublie URL: https://publications.polymtl.ca/3564/
Journal Title: Metabolites (vol. 8, no. 1)
Publisher: MDPI
DOI: 10.3390/metabo8010018
Official URL: https://doi.org/10.3390/metabo8010018
Date Deposited: 09 Mar 2020 11:14
Last Modified: 24 Nov 2022 15:56
Cite in APA 7: Laflaquière, B., Leclercq, G., Choey, C., Chen, J., Peres, S., Ito, C., & Jolicoeur, M. (2018). Identifying biomarkers of Wharton's Jelly mesenchymal stromal cells using a dynamic metabolic model: the cell passage effect. Metabolites, 8(1). https://doi.org/10.3390/metabo8010018

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