title: Regulation of mouse microglia activation and effector functions by bone marrow-derived mesenchymal stem cells.
abstract: Mesenchymal stems or stromal cells (MSCs) are rare multipotent cells with potent regenerative and immunomodulatory properties. Microglial cells (MGs) are specialized tissue macrophages of the central nervous system (CNS) that continuously survey their environment with highly motile extensions. Recently, several studies have shown that MSCs are capable of reprogramming microglia into an "M2-like" phenotype characterized by increased phagocytic activity and upregulated expression of anti-inflammatory mediators in vitro. However, the precise polarization states of microglia in the presence of MSCs under physiological or under inflammatory conditions remain largely unknown. In this study, we found that MSCs induce a mixed microglia phenotype defined as Arg1-high, CD86-high, CD206-high, IL-10-high, PGE2-high, MCP-1/CCL2-high, IL-1β-moderate, NALP-3-low, and TNF-α-low cells. These MSC-elicited MGs have high phagocytic activity and antigen-presenting ability. Lipopolysaccharide is able to shape this microglia phenotype quantitatively, but not qualitatively in the presence of MSCs. This unique polarization state resembles a novel regulatory microglia phenotype, which might contribute to the resolution of inflammation and to tissue repair in the CNS.
authors.affiliation: 1 Laboratory of Molecular Cell Biology, Institute of Molecular Pharmacology, Research Center for Natural Sciences , Hungarian Academy of Sciences, Budapest, Hungary .
authors.forename: Beáta
authors.initials: B
authors.lastname: Hegyi
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Környei
authors.forename: Szilamér
authors.initials: S
authors.lastname: Ferenczi
authors.forename: Rebeka
authors.initials: R
authors.lastname: Fekete
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Kudlik
authors.forename: Krisztina J
authors.initials: KJ
authors.lastname: Kovács
authors.forename: Emília
authors.initials: E
authors.lastname: Madarász
authors.forename: Ferenc
authors.initials: F
authors.lastname: Uher
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology* / Q000378:metabolism; D018613:Microscopy, Confocal; D010587:Phagocytosis / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016753:Interleukin-10