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The experimental application of human embryonic stem cell\u2010derived MSC (ES\u2010MSC) increased rapidly and showed promising results, in vitro and in vivo. However, possible therapeutic effects of human ES\u2010MSC and their EVs on Thioacetamide (TAA)\u2010induced chronic liver injury have not been evaluated yet. Our data indicated that human ES\u2010MSC can significantly suppress the proliferation of peripheral blood mononuclear cells compared to bone marrow (BM)\u2010MSC and adipose (AD)\u2010MSC. Moreover, ES\u2010MSC increased the secretion of anti\u2010inflammatory cytokines (i.e., TGF\u2010\u03b2 and IL\u201010) and decreased IFN\u2010\u03b3, compared to other MSCs. ES\u2010MSC EVs demonstrated immunomodulatory activities comparable to parental cells and ameliorated cirrhosis in TAA\u2010induced chronic rat liver injury, that is, reduction in fibrosis and collagen density, necrosis, caspase density, portal vein diameter, and transaminitis. The gene expression analyses also showed upregulation in collagenases (<jats:italic>MMP9<\/jats:italic> and <jats:italic>MMP13<\/jats:italic>), anti\u2010apoptotic gene (<jats:italic>BCL\u20102<\/jats:italic>) and anti\u2010inflammatory cytokines (<jats:italic>TGF\u2010\u03b21<\/jats:italic> and IL\u201010) and down\u2010regulation of major contributors to fibrosis (<jats:italic>Col1\u03b1<\/jats:italic>, <jats:italic>\u03b1SMA,<\/jats:italic> and <jats:italic>TIMP1<\/jats:italic>), pro\u2010apoptotic gene (<jats:italic>BAX<\/jats:italic>) and pro\u2010inflammatory cytokines (TNF\u03b1 and <jats:italic>IL\u20102<\/jats:italic>) following treatment with ES\u2010MSC and ES\u2010MSC\u2010EV. These results demonstrated that human ES\u2010MSC and ES\u2010MSC EV as an off\u2010the\u2010shelf product, that needs further assessment to be suggested as an allogeneic product for therapeutic applications for liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.26413","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T00:09:05Z","timestamp":1513987745000},"page":"9330-9344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Extracellular vesicles derived from human embryonic stem cell\u2010MSCs ameliorate cirrhosis in thioacetamide\u2010induced chronic liver injury"],"prefix":"10.1002","volume":"233","author":[{"given":"Soura","family":"Mardpour","sequence":"first","affiliation":[{"name":"Tissue engineering and Applied Cell Sciences Department School of Advanced Technologies in Medicine Tehran University of Medical Sciences Tehran Iran"},{"name":"Department of Stem Cells 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