title: Tumor necrosis factor alpha promotes the expression of immunosuppressive proteins and enhances the cell growth in a human bone marrow-derived stem cell culture.
abstract: Mesenchymal stem cells (MSCs) are widely used in experimental treatments for various conditions that involve normal tissue regeneration via inflammatory repair. It is known that MSCs can secrete multiple soluble factors and suppress inflammation. Even though the effect of MSCs on inflammation has been extensively studied, the effect of inflammation on MSCs is poorly understood. One of the major cytokines released at the site of inflammation is tumor necrosis factor alpha (TNF-α) which is known to induce MSC invasion and proliferation. Therefore, we wanted to test the effects of TNF-α exposure on MSCs derived from human bone marrow. We found, as expected, that cell proliferation was significantly enhanced during TNF-α exposure. However, according to the cell surface marker analysis, the intensity of several antigens in the minimum criteria panel for MSCs proposed by International Society of Cellular Therapy (ISCT) was decreased dramatically, and in certain cases, the criteria for MSCs were not fulfilled. In addition, TNF-α exposure resulted in a significant but transient increase in human leukocyte antigen and CD54 expression. Additional proteomic analysis by two-dimensional difference gel electrophoresis and mass spectrometry revealed three proteins whose expression levels decreased and 8 proteins whose expression levels increased significantly during TNF-α exposure. The majority of these proteins could be linked to immunosuppressive and signalling pathways. These results strongly support reactive and immunosuppressive activation of MSCs during TNF-α exposure, which might influence MSC differentiation stage and capacity.
authors.affiliation: Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. johanna.miettinen@oulu.fi
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Miettinen
authors.forename: Mika
authors.initials: M
authors.lastname: Pietilä
authors.forename: Riikka J
authors.initials: RJ
authors.lastname: Salonen
authors.forename: Steffen
authors.initials: S
authors.lastname: Ohlmeier
authors.forename: Kari
authors.initials: K
authors.lastname: Ylitalo
authors.forename: Heikki V
authors.initials: HV
authors.lastname: Huikuri
authors.forename: Petri
authors.initials: P
authors.lastname: Lehenkari
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000276:immunology / Q000503:physiopathology; D018124:Receptors, Tumor Necrosis Factor / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha