{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:28:54Z","timestamp":1793824134322,"version":"4.6.1"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T00:00:00Z","timestamp":1402358400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T00:00:00Z","timestamp":1402358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Mesenchymal stem cell-conditioned medium (MSC-CM) has been shown to have protective effects against various cellular-injury models. This mechanism of protection, however, has yet to be elucidated. Recently, exosomes were identified as the active component in MSC-CM. The aim of this study is to investigate the effect of MSC-derived exosomes in an established carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)-induced liver injury mouse model. This potential effect is then validated by using <jats:italic>in vitro<\/jats:italic> xenobiotic-induced liver-injury assays: (1) acetaminophen (APAP)- and (2) hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>)-induced liver injury.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>The exosomes were introduced concurrent with CCl<jats:sub>4<\/jats:sub> into a mouse model through different routes of administration. Biochemical analysis was performed based on the blood and liver tissues. Subsequently the exosomes were treated in APAP and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-toxicants with <jats:italic>in vitro<\/jats:italic> models. Cell viability was measured, and biomarkers indicative of regenerative and oxidative biochemical responses were determined to probe the mechanism of any hepatoprotective activity observed.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>In contrast to mice treated with phosphate-buffered saline, CCl<jats:sub>4<\/jats:sub> injury in mice was attenuated by concurrent-treatment exosomes, and characterized by an increase in hepatocyte proliferation, as demonstrated with proliferating cell nuclear antigen (PCNA) elevation. Significantly higher cell viability was demonstrated in the exosomes-treated group compared with the non-exosome-treated group in both injury models. The higher survival rate was associated with upregulation of the priming-phase genes during liver regeneration, which subsequently led to higher expression of proliferation proteins (PCNA and cyclin D1) in the exosomes-treated group. Exosomes also inhibited the APAP- and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced hepatocytes apoptosis through upregulation of Bcl-<jats:sub>xL<\/jats:sub> protein expression. However, exosomes do not mitigate hepatocyte injury via modulation of oxidative stress.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>In summary, these results suggest that MSC-derived exosomes can elicit hepatoprotective effects against toxicants-induced injury, mainly through activation of proliferative and regenerative responses.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/scrt465","type":"journal-article","created":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T09:05:21Z","timestamp":1402391121000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":495,"title":["Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models"],"prefix":"10.1186","volume":"5","author":[{"given":"Cheau Yih","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruenn Chai","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yock Young","family":"Dan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai-Kiang","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Kiat","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,6,10]]},"reference":[{"key":"377_CR1","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1096\/fasebj.10.11.8836038","volume":"10","author":"SS Thorgeirsson","year":"1996","unstructured":"Thorgeirsson SS: Hepatic stem cells in liver regeneration. 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