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The immunomodulatory properties of adipose mesenchymal stem cell‐derived exosomes are induced by inflammatory cytokines
Author(s) -
Domenis Rossana,
Quaglia Sara,
Cifù Adriana,
Pistis Cinzia,
Fabris Martina,
Moretti Massimo,
Vicario Annalisa,
Niazi Kayvan R.,
Curcio Francesco
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.981.5
Subject(s) - microvesicles , mesenchymal stem cell , microbiology and biotechnology , paracrine signalling , exosome , stem cell , cd80 , immune system , flow cytometry , viability assay , biology , chemistry , cd40 , immunology , cell , microrna , in vitro , biochemistry , cytotoxic t cell , receptor , gene
The predominant mechanism by which adipose mesenchymal stem cells (AMSCs) participate to tissue repair is through a paracrine activity and their communication with the inflammatory microenvironment is essential part of this process. This hypothesis has been strengthened by the recent discovery that stem cells release not only soluble factors but also extracellular vesicles, which elicit similar biological activity to the stem cells themselves. The most prominent of the extracellular vesicles are exosomes, that through the delivery and the transfer of protein, bio‐active lipid and nucleic acid cargo, are able to induce phenotypic and functional changes in the recipient cells that promote the activation of regenerative programs. The purpose of this study is to investigate the immunomodulatory properties of exosomes released from AMSCs under stimulation with inflammatory cytokines. Methods AMSCs were treated with different concentration of INFγ+TNFα for 48h and then proliferation/viability was measured by trypan blue exclusion count, expression of IDO enzyme was evaluated by flow cytometry and release of PGE2 by ELISA. Exosomes were isolated from AMSCs supernatants by polymer precipitation method (Exoquick). To evaluate their immune‐regulatory properties, CD14+ monocytes were treated, during their differentiation into M1 macrophages, with AMSCs‐derived exosomes. After treatment, macrophages were characterized for the expression of CD80 (M1 expression marker) or CD163 (M2 expression marker) by flow cytometry. Results Pro‐inflammatory INFγ+TNFα cytokines decreased AMSCs proliferation rate, while viability was not affected, and increased the expression of the immunosuppressive IDO enzyme and the release of PGE2 in dose‐dependent manner. Only exosomes released from cytokines‐treated cells were able to significantly reverse the M1 phenotype of macrophages indicating a polarization towards the M2 phenotype. Conclusions The treatment with inflammatory cytokines increase the immunosuppressive and anti‐inflammatory potential of AMSCs‐derived exosomes, which became able to shift macrophages from M1 to M2 phenotype. This suggests that the immunomodulatory properties of AMSCs‐derived exosomes may be not constitutive but are instead induced by the inflammatory microenvironment.