{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T13:59:02Z","timestamp":1773842342845,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":163,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["15545342"],"award-info":[{"award-number":["15545342"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["23K1500200"],"award-info":[{"award-number":["23K1500200"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["21K07998"],"award-info":[{"award-number":["21K07998"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["23K15063"],"award-info":[{"award-number":["23K15063"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["23K0740900"],"award-info":[{"award-number":["23K0740900"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["22K07954"],"award-info":[{"award-number":["22K07954"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["19H03632"],"award-info":[{"award-number":["19H03632"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["23K24313"],"award-info":[{"award-number":["23K24313"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    In recent years, liver regeneration therapy using mesenchymal stem cells (MSC) has been investigated as an alternative therapy for end\u2010stage liver diseases. Among these MSCs, multilineage\u2010differentiating stress enduring (Muse) cells are reported to be effective in mouse models. The present study investigated the safety and effectiveness of Muse cell transplantation in large animal models of hepatic fibrosis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Muse cells and MSC were prepared from bone marrow cells of male mini pigs (G\u00f6ttingen strain). Recipients mini pigs (female G\u00f6ttingen strain) were repeatedly administered with carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) intraperitoneally for 12 weeks to induce liver fibrosis. Thereafter, either Muse cells or MSCs were transplanted intravenously. After the cell transplantation, laboratory tests, vital signs, and liver histology were evaluated (Muse cell group (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096), MSC group (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096), and vehicle group (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097)).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Liver fibrogenesis was successfully induced after 12 weeks of CCl\n                    <jats:sub>4<\/jats:sub>\n                    administration. Engraftment of transplanted cells and differentiation into hepatocytes were confirmed in recipients\u2019 liver. In Muse cell group, significant increase of serum albumin (Alb) level was observed at 4 weeks compared to those of control groups (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009 &lt; 0.05). Hepatic proliferating cell nuclear antigen (PCNA) positive cells were significantly increased in the Muse cell group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009 &lt; 0.05). Hepatic fibrogenesis at 12 weeks after transplantation were significantly improved in Muse cell group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009 &lt; 0.05). Alpha\u2010smooth muscle actin (\u03b1\u2010SMA) immunostaining revealed significant decrease in liver from Muse cell transplanted recipients. No serious adverse effects were observed.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Muse cell transplantation was safe and effective in large animal models of hepatic fibrosis. The positive effects were observed in namely 4 weeks after transplantation. Since biochemical as well as histological improvements were demonstrated, future studies including establishing ideal administration protocol seem to be feasible as a preclinical study.\n                  <\/jats:p>","DOI":"10.1155\/sci\/6699571","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:35:44Z","timestamp":1749807344000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Safety and Effectiveness of Muse Cell Transplantation in a Large\u2010Animal Model of Hepatic Fibrosis"],"prefix":"10.1155","volume":"2025","author":[{"given":"Taketo","family":"Nishina","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9355-1837","authenticated-orcid":false,"given":"Hiroaki","family":"Haga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Wakao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keita","family":"Maki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Katsumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko 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