title: Mesenchymal Stem Cell-Derived Microvesicles Modulate Lipopolysaccharides-Induced Inflammatory Responses to Microglia Cells.
abstract: Microglia cells are the central nervous system immune cells and have been pointed out as the main mediators of the inflammation leading to neurodegenerative disorders. Mesenchymal stromal cells (MSCs) are a heterogeneous population of cells with very high self-renewal properties and uncomplicated in vitro culture. Research has shown that MSCs have the capacity to induce tissue regeneration and reduce inflammation. Studies demonstrated that MSCs have complex paracrine machineries involving shedding of cell-derived microvesicles (MVs), which entail part of the regulatory and regenerative activity of MSCs, as observed in animal models. We proposed MSC-derived MVs as potent regulators of microglia activation and used an in vitro model of stimulation for BV-2 cells, a microglia cell line, with lipopolysaccharides (LPS). Here we demonstrated that presence of MSCs-derived MVs (MSC-MVs) prevents Tumor necrosis factor-α, Interleukin (IL)-1β and IL-6 upregulation by BV-2 cells and primary microglia cells toward LPS. Also, inducible isoform of nitric oxide synthases and Prostaglandin-endoperoxide synthase 2 upregulation were hampered in presence of MSC-MVs. Higher levels of the M2 microglia marker chemokine ligand-22 were detectable in BV-2 cells after coculture with MSC-MVs in presence and absence of LPS. Moreover, upregulation of the activation markers CD45 and CD11b by BV-2 cells was prevented when cocultured with MSC-MVs. Furthermore, MSC-MVs suppressed the phosphorylation of the extracellular signal kinases 1/2, c-Jun N-terminal kinases and the p38 MAP kinase (p38) molecules. Consequently, MSC-MVs might represent a modulator of microglia activation with future therapeutic impact. Stem Cells 2017;35:812-823.
authors.affiliation: Immunology Department, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.|Institute for Clinical Immunology, Department of Immune Diagnostic, University of Leipzig, Leipzig, Germany.
authors.forename: Yarúa
authors.initials: Y
authors.lastname: Jaimes
authors.affiliation: Institute for Clinical Immunology, Department of Immune Diagnostic, University of Leipzig, Leipzig, Germany.
authors.forename: Yahaira
authors.initials: Y
authors.lastname: Naaldijk
authors.affiliation: Institute for Clinical Immunology, Department of Immune Diagnostic, University of Leipzig, Leipzig, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wenk
authors.affiliation: Immunology Department, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Leovsky
authors.affiliation: Immunology Department, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.|Institute for Clinical Immunology, Department of Immune Diagnostic, University of Leipzig, Leipzig, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Emmrich
mesh_terms: D000818:Animals; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; C491899:Fas protein, mouse; D008070:Lipopolysaccharides; D019014:fas Receptor
keywords: Inflammation; Mesenchymal stem cells; Microglia; Microvesicles; Neurodegeneration