Prevention Of Acute Lung Injury In Mice By Human Mesenchymal Stem Cells Regulating Macrophage Polarization

Background:Acute Lung Injury(ALI)is a outcome of lung excessive inflammation.Human mesenchymal stem cell(hMSC)has rencently been considered to attenuate ALI by paracrine.Macrophages polarization play a key role in response,evolution and resolution of inflammation.In this study,we reseached the relationship between hMSC and macrophage polarization.Methods:ALI of C57BL/6 mouse were induced by intratracheally LPS instillation.Mouse were randomly divided into 3 groups(n=5):PBS control(P)group,LPS(L)group,hMSC(M)group.The lungs and bronchoalveolar lavage fluid were collected 24 hours after LPS instillation for HE slices,inflammatory cytokines detection.RAW264.7 macrophages were seeded in 6-well plate divided into 3 groups:Control(C)group,LPS+IFN-γ stimuLated(L)group,LPS+IFN-y stimuLated cocuLtured with hMSC(M)group.The medium supernatant and macrophages were collected 24 hours after stimulation for inflammatory cytokines detection and macrophage M1/M2 polarization markers examination.Results:(1)hMSC could attenuate the inflammatory response in LPS-induced ALI mice,improve alveoli capillary leakage and downregulate iNOS protein expression of alveolar macrophages.(2)Cocultured hMSC decreased proinflammatory cytokines secreted by stimulated RAW264.7 macrophages in vitro.Meanwhile,cocultured hMSC downregulated macrophage M1 polarization and upregulate M2 polarization through mRNA transcription,protein translation and cell phenotype.ConclusionHuman mesenchymal stem cells could attenuate ALI by suppressing macrophage M1 polarization and promoting M2 polarization.The development of stem cells research provide a new therapy in the future.