{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:21:42Z","timestamp":1792682502319,"version":"4.5.0"},"reference-count":38,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24bk0104152"],"award-info":[{"award-number":["JP24bk0104152"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    Metabolic dysfunction\u2013associated steatotic liver disease (MASLD) is the most common chronic liver disorder and can progress to steatohepatitis and fibrosis; although approved pharmacotherapies for metabolic dysfunction\u2013associated steatohepatitis (MASH) with fibrosis remain limited. Autologous chemically induced liver progenitor (CLiP) cells, generated from mature hepatocytes without genetic modification, have shown therapeutic promise in rodents, but their efficacy has not been tested in large animals. Six female Clawn miniature pigs (15\u201342 kg) were fed a high-fat, high-cholesterol diet to induce MASLD with biopsy-proven fibrosis (Brunt stage \u22651). Animals were assigned to CLiP transplantation (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 3) or saline control (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 3). Autologous CLiPs (5 \u00d7 10\n                    <jats:sup>7<\/jats:sup>\n                    ) were generated from laparoscopically resected liver wedges, expanded\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    , and infused intraportally. Safety was assessed by monitoring, liver function tests, and lipid profiles. Efficacy was evaluated 1 month later by blinded histology and immunohistochemistry. CLiP transplantation was feasible and well tolerated. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) showed minimal changes in both groups, but total cholesterol and triglycerides decreased in treated pigs and increased in controls. Histologically, two of three CLiP-treated livers regressed from Brunt stage 1 to 0, with resolution of steatosis and reduced stellate cell activation, whereas controls showed no regression. These findings support CLiP therapy as a regenerative option for MASLD.\n                  <\/jats:p>","DOI":"10.1177\/09636897261446732","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:53:09Z","timestamp":1780476789000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Autologous chemically induced liver progenitor cell transplantation ameliorates steatosis and fibrosis in a preclinical miniature pig model of metabolic dysfunction\u2013associated fatty liver disease: A pilot study"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3078-725X","authenticated-orcid":false,"given":"Takanobu","family":"Hara","sequence":"first","affiliation":[{"name":"Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Maruya","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-9904","authenticated-orcid":false,"given":"Daisuke","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1577-6587","authenticated-orcid":false,"given":"Hajime","family":"Matsushima","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 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, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Ochiya","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine, Tokyo Medical University, Shinjuku-ku, 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, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56910-x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-91312-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29367"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.03.039"},{"issue":"12","key":"e_1_3_2_9_2","article-title":"NN9931-4296 investigators. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis","volume":"384","author":"Newsome PN","year":"2021","unstructured":"Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal AJ, Sejling AS, Harrison SA. NN9931-4296 investigators. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384(12):1113\u201324.","journal-title":"N Engl J Med"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.284"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i36.10253"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6135.2004.0340.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000266"},{"issue":"4","key":"e_1_3_2_14_2","article-title":"Clinical hepatocyte transplantation: what is next","volume":"4","author":"Squires JE","year":"2017","unstructured":"Squires JE, Soltys KA, McKiernan P, Squires RH, Strom SC, Fox IJ, Soto-Gutierrez A. Clinical hepatocyte transplantation: what is next. 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Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis. Regen Ther. 2022;21: 574\u201383.","journal-title":"Regen Ther"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2023.06.005"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/jhbp.12046"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/jhbp.1425"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat.57703"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0313312"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-022-01869-5"},{"issue":"6","key":"e_1_3_2_34_2","article-title":"Nonalcoholic steatohepatitis clinical research network","volume":"41","author":"Kleiner DE","year":"2005","unstructured":"Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, et al. Nonalcoholic steatohepatitis clinical research network. 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