Regulation of mouse microglia activation and effector functions by bone marrow-derived mesenchymal stem cells

Hegyi, Beáta and Környei, Zsuzsanna and Ferenczi, Szilamér and Fekete, Rebeka and Kudlik, Gyöngyi and Kovács J., Krisztina and Madarász, Emília and Uher, Ferenc (2014) Regulation of mouse microglia activation and effector functions by bone marrow-derived mesenchymal stem cells. STEM CELLS AND DEVELOPMENT, 23 (21). pp. 2600-2612. ISSN 1547-3287

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Abstract

Mesenchymal stem or stromal cells (MSCs) are rare multipotent cells with potent regenerative and immunomodulatory properties. Microglial cells 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 Arg-1-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 microglial cells have high phagocytic activity and antigen-presenting ability. Lipopolysaccharide (LPS) 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.

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