Mesenchymal Stem Cells Induce Suppressive Macrophages Through Phagocytosis in a Mouse Model of Asthma. (14th March 2016)

• Record Type: Journal Article
• Authors: Braza, Faouzi; Dirou, Stéphanie; Forest, Virginie; Sauzeau, Vincent; Hassoun, Dorian; Chesné, Julie; Cheminant-Muller, Marie-Aude; Sagan, Christine; Magnan, Antoine; Lemarchand, Patricia
• Is Part Of: Stem cells. Volume 34:Number 7(2016:Jul.)
• Page Start: 1836
• Page End: 1845
• Publication Date: 2016-03-14
• Subjects: House dust mite asthma -- Mesenchymal stem cells -- M2 macrophage -- Airway hyper-responsiveness -- Phagocytosis -- Airway smooth muscle contraction; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2344
• Languages: English
• ISSNs: 1066-5099

Abstract

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 labeled 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. Abstract : Lung macrophages have been cell-sorted from lung cell suspensions, 24 hours after intravenous injection of PKH26 + mesenchymal stem cells (MSCs). PKH26 staining is characterized by incorporation of red fluorescent molecules into the cell membrane and induces intense and reproducible fluorescence. Lung macrophages show PKH26 + (red) labeling, suggesting that they had in vivo phagocyted the PKH26 + MSCs.