title: Aging bone marrow mesenchymal stromal cells have altered membrane glycerophospholipid composition and functionality.
abstract: Human mesenchymal stem/stromal cells (hMSC) are increasingly used in advanced cellular therapies. The clinical use of hMSCs demands sequential cell expansions. As it is well established that membrane glycerophospholipids (GPL) provide precursors for signaling lipids that modulate cellular functions, we studied the effect of the donor's age and cell doublings on the GPL profile of human bone marrow MSC (hBMSC). The hBMSCs, which were harvested from five young and five old adults, showed clear compositional changes during expansion seen at the level of lipid classes, lipid species, and acyl chains. The ratio of phosphatidylinositol to phosphatidylserine increased toward the late-passage samples. Furthermore, 20:4n-6-containing species of phosphatidylcholine and phosphatidylethanolamine accumulated while the species containing monounsaturated fatty acids (FA) decreased during passaging. Additionally, in the total FA pool of the cells, 20:4n-6 increased, which happened at the expense of n-3 polyunsaturated FAs, especially 22:6n-3. The GPL and FA correlated with the decreased immunosuppressive capacity of hBMSCs during expansion. Our observations were further supported by alterations in the gene expression levels of several enzymes involved in lipid metabolism and immunomodulation. The results show that extensive expansion of hBMSCs harmfully modulates membrane GPLs, affecting lipid signaling and eventually impairing functionality.
authors.affiliation: Advanced Therapies and Product Development, Finnish Red Cross Blood Service, Helsinki, Finland.
authors.forename: Lotta
authors.initials: L
authors.lastname: Kilpinen
authors.affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Feven
authors.initials: F
authors.lastname: Tigistu-Sahle
authors.affiliation: Advanced Therapies and Product Development, Finnish Red Cross Blood Service, Helsinki, Finland; Institute of Biomedicine, Anatomy, University of Helsinki, Helsinki, Finland.
authors.forename: Sofia
authors.initials: S
authors.lastname: Oja
authors.affiliation: Department of Bioscience and Nutrition, Karolinska Institute, Stockholm, Sweden; Research Program of Molecular Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Dario
authors.initials: D
authors.lastname: Greco
authors.affiliation: Research Program of Molecular Medicine, University of Helsinki, Helsinki, Finland; Haartman Institute, Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Amarjit
authors.initials: A
authors.lastname: Parmar
authors.affiliation: Research Program of Molecular Medicine, University of Helsinki, Helsinki, Finland; Haartman Institute, Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Saavalainen
authors.affiliation: Advanced Therapies and Product Development, Finnish Red Cross Blood Service, Helsinki, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Nikkilä
authors.affiliation: Advanced Therapies and Product Development, Finnish Red Cross Blood Service, Helsinki, Finland; Institute of Biomedicine, Anatomy, University of Helsinki, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Korhonen
authors.affiliation: Institute of Biomedicine; Institute of Clinical Medicine, Division of Surgery, Universtiy of Oulu, Oulu, Finland; Clinical Research Centre, Department of Surgery and Intensive Care, Oulu, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Lehenkari
authors.affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Käkelä
authors.affiliation: Advanced Therapies and Product Development, Finnish Red Cross Blood Service, Helsinki, Finland.
authors.forename: Saara
authors.initials: S
authors.lastname: Laitinen
mesh_terms: D000375:Aging / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D002849:Chromatography, Gas; D004281:Docosahexaenoic Acids / Q000378:metabolism; D020404:Glycerophospholipids / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D013058:Mass Spectrometry; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D016615:Telomere / Q000235:genetics
chemical_list: D020404:Glycerophospholipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid