title: Lipidomics of Mesenchymal Stromal Cells: Understanding the Adaptation of Phospholipid Profile in Response to Pro-Inflammatory Cytokines.
abstract: Mesenchymal stromal cells (MSCs) present anti-inflammatory properties and are being used with great success as treatment for inflammatory and autoimmune diseases. In clinical applications MSCs are subjected to a strong pro-inflammatory environment, essential to their immunosuppressive action. Despite the wide clinical use of these cells, how MSCs exert their effect remains unclear. Several lipids are known to be involved in cell's signaling and modulation of cellular functions. The aim of this paper is to examine the variation in lipid profile of MSCs under pro-inflammatory environment, induced by the presence of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), using the most modern lipidomic approach. Major changes in lipid molecular profile of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), lysoPC (LPC), and sphingomyelin (SM) classes were found. No changes were observed in the phosphatidylinositol (PI) profile. The levels of PC species with shorter fatty acids (FAs), mainly C16:0, decreased under pro-inflammatory stimuli. The level of PC(40:6) also decreased, which may be correlated with enhanced levels of LPC(18:0), which is known to be an anti-inflammatory LPC, observed in MSCs subjected to TNF-α and IFN-γ. Simultaneously, the relative amounts of PC(36:1) and PC(38:4) increased. TNF-α and IFN-γ also enhanced the levels of PE(40:6) and decreased the levels of PE(O-38:6). Higher expression of PS(36:1) and SM(34:0) along with a decrease in PS(38:6) levels were observed. These results indicate that lipid metabolism and signaling are modulated during MSCs activation, which suggests that lipids may be involved in MSCs functional and anti-inflammatory activities.
authors.affiliation: Mass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Ana Margarida
authors.initials: AM
authors.lastname: Campos
authors.affiliation: Mass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Maciel
authors.affiliation: Mass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Ana S P
authors.initials: AS
authors.lastname: Moreira
authors.affiliation: Mass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Bebiana
authors.initials: B
authors.lastname: Sousa
authors.affiliation: Mass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Melo
authors.affiliation: Mass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Domingues
authors.affiliation: Cell2B Advanced Therapeutics SA, Biocant Park Núcleo 04 Lote 4 A, Cantanhede, Portugal.
authors.forename: Liliana
authors.initials: L
authors.lastname: Curado
authors.affiliation: Cell2B Advanced Therapeutics SA, Biocant Park Núcleo 04 Lote 4 A, Cantanhede, Portugal.
authors.forename: Brígida
authors.initials: B
authors.lastname: Antunes
authors.affiliation: Mass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: M Rosário M
authors.initials: MR
authors.lastname: Domingues
authors.affiliation: Cell2B Advanced Therapeutics SA, Biocant Park Núcleo 04 Lote 4 A, Cantanhede, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Santos
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D016207:Cytokines / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects*; D013058:Mass Spectrometry; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D055432:Metabolomics; D010743:Phospholipids / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult
chemical_list: D016207:Cytokines; D005227:Fatty Acids; D018836:Inflammation Mediators; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma