{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:21:41Z","timestamp":1792682501892,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20bm0404042"],"award-info":[{"award-number":["20bm0404042"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["22bk0104152"],"award-info":[{"award-number":["22bk0104152"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Hepato Biliary Pancreat"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Numerous chemical reprogramming techniques have been reported, rendering them applicable to regenerative medicine research. The aim of our study was to evaluate the therapeutic potential of human CLiP derived from clinical specimens transplanted into a nonalcoholic steatohepatitis (NASH) mouse model of liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We successfully generated chemically induced liver progenitor (CLiP), which exhibited progenitor\u2010like characteristics, through stimulation with low\u2010molecular\u2010weight compounds. We elucidated their cell differentiation ability and therapeutic effects. However, the therapeutic efficacy of human CLiP generated from clinical samples on liver fibrosis, such as liver cirrhosis, remains unproven.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following a 4\u2009week period, transplanted human CLiP in the NASH model differentiated into mature hepatocytes and demonstrated suppressive effects on liver injury markers (i.e., aspartate transaminase and alanine transaminase). Although genes related to inflammation and fat deposition did not change in the human CLiP transplantation group, liver fibrosis\u2010related factors (Acta2 and Col1A1) showed suppressive effects on gene expression following transplantation, with approximately a 60% reduction in collagen fibers. Importantly, human CLiP could be efficiently induced from hepatocytes isolated from the cirrhotic liver, underscoring the feasibility of using autologous hepatocytes to produce human CLiP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings demonstrate the effectiveness of human CLiP transplantation as a viable cellular therapy for liver fibrosis, including NASH liver. These results hold promise for the development of liver antifibrosis therapy utilizing human CLiP within the field of liver regenerative medicine.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jhbp.12046","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T07:24:35Z","timestamp":1721287475000},"page":"697-704","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy of chemically induced human hepatic progenitor cells from diseased liver against nonalcoholic steatohepatitis model"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-9904","authenticated-orcid":false,"given":"Daisuke","family":"Miyamoto","sequence":"first","affiliation":[{"name":"Department of Surgery Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihito","family":"Matsuguma","sequence":"additional","affiliation":[{"name":"Department of Surgery Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Surgery Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"},{"name":"Department of Clinical Laboratory NHO Nagasaki Medical Center  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Miyoshi","sequence":"additional","affiliation":[{"name":"Department of Surgery Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanobu","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Surgery Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Matsushima","sequence":"additional","affiliation":[{"name":"Department of Surgery Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2932-4300","authenticated-orcid":false,"given":"Akihiko","family":"Soyama","sequence":"additional","affiliation":[{"name":"Department of Surgery Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Ochiya","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Therapy Research, Medical Research Institute Tokyo Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Transfusion and Cell Therapy Unit Nagasaki University Hospital  Nagasaki Japan"},{"name":"Department of Hematology Atomic Bomb Disedase Institute, Nagasaki University  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7876-0152","authenticated-orcid":false,"given":"Susumu","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Department of Surgery Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-014-0973-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i15.1622"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba5573"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20484"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21010178"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-021-00132-4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03143-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072217"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-011-0106-4"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.32"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.142"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44534"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.06.006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/3975689","article-title":"Development of bifunctional three\u2010dimensional cysts from chemically induced liver progenitors","volume":"2019","author":"Huang Y","year":"2019","journal-title":"Stem Cells Int"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27773"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.10.007"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2022.11.001"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13609"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-022-01869-5"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/iep.12008"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)80412-2"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.05.150"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00128.2002"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/795385"}],"container-title":["Journal of Hepato-Biliary-Pancreatic Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jhbp.12046","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T16:08:37Z","timestamp":1734365317000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jhbp.12046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,18]]},"references-count":24,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/jhbp.12046"],"URL":"https:\/\/doi.org\/10.1002\/jhbp.12046","archive":["Portico"],"relation":{},"ISSN":["1868-6974","1868-6982"],"issn-type":[{"value":"1868-6974","type":"print"},{"value":"1868-6982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,18]]},"assertion":[{"value":"2024-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}