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Mesenchymal stem cells induce suppressive macrophages through phagocytosis in a mouse model of asthma.
Stem Cells. 2016 Feb 17;
Authors: Braza F, Dirou S, Forest V, Sauzeau V, Hassoun D, Chesné J, Cheminant-Muller MA, Sagan C, Magnan A, Lemarchand P
Abstract
Mesenchymal stem cell (MSC) immunosuppressive functions make them attractive candidates for anti-inflammatory therapy in allergic asthma. However the mechanisms by which they ensure therapeutic effects remain to be elucidated. In an acute mouse model of house dust mite (Der f)-induced asthma, one i.v. MSC injection was sufficient to normalize and stabilize lung function in Der f-sensitized mice as compared to control mice. MSC injection decreased in vivo airway responsiveness and decreased ex vivo carbachol-induced bronchial contraction, maintaining bronchial expression of the inhibitory type 2 muscarinic receptor. To evaluate in vivo MSC survival, MSCs were labelled with PKH26 fluorescent marker prior to i.v. injection, and 1 to 10 days later total lungs were digested to obtain single-cell suspensions. 91.5?±?2.3% and 86.6?±?6.3% of the recovered PKH26(+) lung cells expressed specific macrophage markers in control and Der f mice respectively, suggesting that macrophages had phagocyted in vivo the injected MSCs. Interestingly, only PKH26(+) macrophages expressed M2 phenotype, while the innate PKH26(-) macrophages expressed M1 phenotype. Finally, the remaining 0.5% PKH26(+) MSCs expressed 10 to 100 fold more COX-2 than before injection, suggesting in vivo MSC phenotype modification. Together, the results of this study indicate that MSCs attenuate asthma by being phagocyted by lung macrophages, which in turn acquire a M2 suppressive phenotype. This article is protected by copyright. All rights reserved.
PMID: 26891455 [PubMed – as supplied by publisher]
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