{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:59:45Z","timestamp":1792162785833,"version":"4.4.0"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T00:00:00Z","timestamp":1682812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IAF\u2212ICP funding","award":["#I1801E0019"],"award-info":[{"award-number":["#I1801E0019"]}]},{"name":"IAF\u2212ICP funding","award":["#H19H6a0026"],"award-info":[{"award-number":["#H19H6a0026"]}]},{"name":"IAF\u2212PP funding","award":["#I1801E0019"],"award-info":[{"award-number":["#I1801E0019"]}]},{"name":"IAF\u2212PP funding","award":["#H19H6a0026"],"award-info":[{"award-number":["#H19H6a0026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mesenchymal stem\/stromal cell small extracellular vesicles (MSC\u2212sEVs) have shown promise in treating a wide range of animal models of various human diseases, which has led to their consideration for clinical translation. However, the possibility of contraindication for MSC\u2212sEV use is an important consideration. One concern is that MSC\u2212sEVs have been shown to induce M2 macrophage polarization, which is known to be pro\u2212fibrotic, potentially indicating contraindication in fibrotic diseases such as liver fibrosis. Despite this concern, previous studies have shown that MSC\u2212sEVs alleviate high\u2212fat diet (HFD)\u2212induced non\u2212alcoholic steatohepatitis (NASH). To assess whether the pro\u2212fibrotic M2 macrophage polarization induced by MSC\u2212sEVs could worsen liver fibrosis, we first verified that our MSC\u2212sEV preparations could promote M2 polarization in vitro prior to their administration in a mouse model of NASH. Our results showed that treatment with MSC\u2212sEVs reduced or had comparable NAFLD Activity Scores and liver fibrosis compared to vehicle\u2212 and Telmisartan\u2212treated animals, respectively. Although CD163+ M2 macrophages were increased in the liver, and serum IL\u22126 levels were reduced in MSC\u2212sEV treated animals, our data suggests that MSC\u2212sEV treatment was efficacious in reducing liver fibrosis in a mouse model of NASH despite an increase in pro\u2212fibrotic M2 macrophage polarization.<\/jats:p>","DOI":"10.3390\/ijms24098092","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T13:54:46Z","timestamp":1682949286000},"page":"8092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["MSC\u2212sEV Treatment Polarizes Pro\u2212Fibrotic M2 Macrophages without Exacerbating Liver Fibrosis in NASH"],"prefix":"10.3390","volume":"24","author":[{"given":"Bin","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4636-8535","authenticated-orcid":false,"given":"Ruenn Chai","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Kian","family":"Sim","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1316-4333","authenticated-orcid":false,"given":"Kong Peng","family":"Lam","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Singapore 138648, Singapore"},{"name":"Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore"},{"name":"School of Biological Sciences, College of Science, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5752-3297","authenticated-orcid":false,"given":"Sai Kiang","family":"Lim","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore"},{"name":"Department of Surgery, YLL School of Medicine, NUS, 5 Lower Kent Ridge Road, Singapore 119074, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. 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