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Extracellular vesicles isolated from human mesenchymal stem cells promote resolution of pulmonary fibrosis
Author(s) -
Shentu Tzu Pin,
Wong Simon,
Espinoza Celia,
CernelcKohan Mateja,
Hagood James
Publication year - 2016
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.30.1_supplement.160.2
Subject(s) - mesenchymal stem cell , pulmonary fibrosis , fibrosis , in vivo , microbiology and biotechnology , myofibroblast , idiopathic pulmonary fibrosis , exosome , chemistry , in vitro , cancer research , microvesicles , medicine , biology , lung , pathology , microrna , biochemistry , gene
The recent discovery of therapeutic applications of extracellular vesicles (EVs) released from human mesenchymal stem cells (hMSCs) has generated interest in their mechanisms of targeting and action. The aim of this study was to explore the role of hMSC‐derived EVs in pulmonary fibrosis. An in vivo efficacy study demonstrated that delivery of hMSC‐EVs (50 μg protein, iv.) at day 14 in mice with pulmonary fibrosis induced by intratracheal bleomycin significantly down‐regulated α‐smooth muscle actin (αSMA) expression and improved histopathological fibrosis, indicating therapeutic effects of these vesicles for established lung fibrosis through modification of the myofibroblastic phenotype; Pretreatment of hMSC‐EVs with antibody to hThy‐1 blocked the effects, suggesting Thy‐1, a cell surface glycoprotein, is essential for the beneficial effects. In vitro studies demonstrated that hMSC‐EVs with membrane‐anchored Thy‐1 display increased cellular uptake by lung fibroblasts in time and dose‐dependent manners as compared to EVs derived from fibroblasts. Removal or blocking of Thy‐1 by phosphatidylinositol specific phospholipase C (PI‐PLC) or anti‐Thy‐1 antibody decreased the uptake of EVs. Cellular uptakes of hMSC‐EVs (10 μg/ml) significantly suppressed TGFb1‐induced pro‐fibrotic gene expression in vitro . Thy‐1 blockade abrogates the rescue effects of hMSC‐EVs. Our novel findings indicate that hMSC–derived EVs exert antifibrotic effects relevant to pulmonary fibrosis, dependent on surface expression of Thy‐1.