title: Mesenchymal stem cells secrete immunologically active exosomes.
abstract: Mesenchymal stem cells (MSCs) have been shown to secrete exosomes that are cardioprotective. Here, we demonstrated that MSC exosome, a secreted membrane vesicle, is immunologically active. MSC exosomes induced polymyxin-resistant, MYD88-dependent secreted embryonic alkaline phosphatase (SEAP) expression in a THP1-Xblue, a THP-1 reporter cell line with an NFκB-SEAP reporter gene. In contrast to lipopolysaccharide, they induced high levels of anti-inflammatory IL10 and TGFβ1 transcript at 3 and 72 h, and much attenuated levels of pro-inflammatory IL1B, IL6, TNFA and IL12P40 transcript at 3-h. The 3-h but not 72-h induction of cytokine transcript was abrogated by MyD88 deficiency. Primary human and mouse monocytes exhibited a similar exosome-induced cytokine transcript profile. Exosome-treated THP-1 but not MyD88-deficient THP-1 cells polarized activated CD4(+) T cells to CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) at a ratio of one exosome-treated THP-1 cell to 1,000 CD4(+) T cells. Infusion of MSC exosomes enhanced the survival of allogenic skin graft in mice and increased Tregs.
authors.affiliation: 1 A*STAR Institute of Medical Biology , Singapore, Singapore .
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Yijun
authors.initials: Y
authors.lastname: Yin
authors.forename: Ruenn Chai
authors.initials: RC
authors.lastname: Lai
authors.forename: Soon Sim
authors.initials: SS
authors.lastname: Tan
authors.forename: Andre Boon Hwa
authors.initials: AB
authors.lastname: Choo
authors.forename: Sai Kiang
authors.initials: SK
authors.lastname: Lim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D055354:Exosomes / Q000276:immunology* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007109:Immunity / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors