{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T11:46:30Z","timestamp":1768736790544,"version":"3.49.0"},"reference-count":214,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mature hepatocytes (MHs) in an adult rodent liver are categorized into the following three subpopulations based on their proliferative capability: type I cells (MH-I), which are committed progenitor cells that possess a high growth capability and basal hepatocytic functions; type II cells (MH-II), which possess a limited proliferative capability; and type III cells (MH-III), which lose the ability to divide (replicative senescence) and reach the final differentiated state. These subpopulations may explain the liver\u2019s development and growth after birth. Generally, small-sized hepatocytes emerge in mammal livers. The cells are characterized by being morphologically identical to hepatocytes except for their size, which is substantially smaller than that of ordinary MHs. We initially discovered small hepatocytes (SHs) in the primary culture of rat hepatocytes. We believe that SHs are derived from MH-I and play a role as hepatocytic progenitors to supply MHs. The population of MH-I (SHs) is distributed in the whole lobules, a part of which possesses a self-renewal capability, and decreases with age. Conversely, injured livers of experimental models and clinical cases showed the emergence of SHs. Studies demonstrate the involvement of SHs in liver regeneration. SHs that appeared in the injured livers are not a pure population but a mixture of two distinct origins, MH-derived and hepatic-stem-cell-derived cells. The predominant cell-derived SHs depend on the proliferative capability of the remaining MHs after the injury. This review will focus on the SHs that appeared in the liver and discuss the significance of SHs in liver regeneration.<\/jats:p>","DOI":"10.3390\/cells12232718","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T07:56:10Z","timestamp":1701071770000},"page":"2718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["\u201cSmall Hepatocytes\u201d in the Liver"],"prefix":"10.3390","volume":"12","author":[{"given":"Toshihiro","family":"Mitaka","sequence":"first","affiliation":[{"name":"Department of Tissue Development and Regeneration, Institute of Regenerative Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3723-7418","authenticated-orcid":false,"given":"Norihisa","family":"Ichinohe","sequence":"additional","affiliation":[{"name":"Department of Tissue Development and Regeneration, Institute of Regenerative Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Tanimizu","sequence":"additional","affiliation":[{"name":"Department of Tissue Development and Regeneration, Institute of Regenerative Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan"},{"name":"Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"ref_1","first-page":"119","article-title":"Classification of cell populations on the basis of their proliferative behavior","volume":"14","author":"Leblond","year":"1964","journal-title":"Natl. Cancer Inst. Monogr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s11894-010-0130-3","article-title":"Intestinal Stem Cells","volume":"12","author":"Umar","year":"2010","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/1523-1747.ep12261462","article-title":"Cell Proliferation in Normal Epidermis","volume":"82","author":"Weinstein","year":"1984","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","unstructured":"Bucher, N.L.R., and Malt, R.A. (1971). Regeneration of Liver and Kidney, Little, Brown and Co."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1001\/archinte.1961.03620030023003","article-title":"\u201cLifespan\u201d of Liver Cells: Autoradiographic study using tritiated thymidine in normal, cirrhotic, and partially hepatectomized rats","volume":"107","author":"MacDONALD","year":"1961","journal-title":"Arch. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/0014-4800(66)90012-8","article-title":"Cell population dynamics in the liver: A review of quantitative morphological techniques applied to the study of physiological and pathological growth","volume":"5","author":"Steiner","year":"1966","journal-title":"Exp. Mol. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S0002-9440(10)64566-X","article-title":"Cellular Origin of Regenerating Parenchyma in a Mouse Model of Severe Hepatic Injury","volume":"157","author":"Braun","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_8","first-page":"535","article-title":"Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine","volume":"139","author":"Lemire","year":"1991","journal-title":"Am. J. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1046\/j.1365-2613.1998.00083.x","article-title":"The current status of primary hepatocyte culture","volume":"79","author":"Mitaka","year":"2002","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/hep.20178","article-title":"2-acetylaminofluorene dose-dependent differentiation of rat oval cells into hepatocytes: Confocal and electron microscopic studies","volume":"39","author":"Nagy","year":"2004","journal-title":"Hepatology"},{"key":"ref_11","first-page":"142","article-title":"Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3\u2032-methyl-4-dimethylaminoazobenzene","volume":"16","author":"Farber","year":"1956","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1055\/s-2004-815561","article-title":"Characterization of the Differentiation Capacity of Rat-Derived Hepatic Stem Cells","volume":"23","author":"Alison","year":"2003","journal-title":"Semin. Liver Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1055\/s-2004-815562","article-title":"Hepatic Stem Cells and Liver Repopulation","volume":"23","author":"Dabeva","year":"2003","journal-title":"Semin. Liver Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/labinvest.3700479","article-title":"The oncofetal protein glypican-3 is a novel marker of hepatic progenitor\/oval cells","volume":"86","author":"Grozdanov","year":"2006","journal-title":"Lab. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000163565","article-title":"An Antigenic Portrait of the Liver during Carcinogenesis","volume":"58","author":"Hixson","year":"1990","journal-title":"Pathobiology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/S0002-9440(10)63221-X","article-title":"Transit-Amplifying Ductular (Oval) Cells and Their Hepatocytic Progeny Are Characterized by a Novel and Distinctive Expression of Delta-Like Protein\/Preadipocyte Factor 1\/Fetal Antigen 1","volume":"164","author":"Jensen","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/hep.510270218","article-title":"Hepatic oval cells express the hematopoietic stem cell marker thy-1 in the rat","volume":"27","author":"Petersen","year":"1998","journal-title":"Hepatology"},{"key":"ref_18","first-page":"1606","article-title":"Activation, proliferation, and differentiation of progenitor cells into hepatocytes in the D-galactosamine model of liver regeneration","volume":"143","author":"Dabeva","year":"1993","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/hep.1840160224","article-title":"Small cell colonies appear in the primary culture of adult rat hepatocytes in the presence of nicotinamide and epidermal growth factor","volume":"16","author":"Mitaka","year":"1992","journal-title":"Hepatology"},{"key":"ref_20","first-page":"383","article-title":"Long-Term Cultivation of Adult Rat Hepatocytes That Undergo Multiple Cell Divisions and Express Normal Parenchymal Phenotypes","volume":"148","author":"Tateno","year":"1996","journal-title":"Am. J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0002-9440(10)64765-7","article-title":"Liver Regeneration in Rats with Retrorsine-Induced Hepatocellular Injury Proceeds through a Novel Cellular Response","volume":"156","author":"Gordon","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1002\/hep.20130","article-title":"Nomenclature of the finer branches of the biliary tree: Canals, ductules, and ductular reactions in human livers","volume":"39","author":"Roskams","year":"2004","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1002\/hep.20214","article-title":"Liver regeneration and repair: Hepatocytes, progenitor cells, and stem cells","volume":"39","author":"Fausto","year":"2004","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/path.1163","article-title":"Hepatic stem cells","volume":"197","author":"Forbes","year":"2002","journal-title":"J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.stem.2020.08.016","article-title":"Epithelial Plasticity during Liver Injury and Regeneration","volume":"27","author":"Gadd","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/bies.20311","article-title":"Jekyll and Hyde: Evolving perspectives on the function and potential of the adult liver progenitor (oval) cell","volume":"27","author":"Knight","year":"2005","journal-title":"BioEssays"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev-pathmechdis-012419-032824","article-title":"Liver Progenitors and Adult Cell Plasticity in Hepatic Injury and Repair: Knowns and Unknowns","volume":"15","author":"Ko","year":"2020","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1053\/j.gastro.2015.08.004","article-title":"Liver Stem Cells: Experimental Findings and Implications for Human Liver Disease","volume":"149","author":"Michalopoulos","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.stem.2014.04.010","article-title":"Stem\/Progenitor Cells in Liver Development, Homeostasis, Regeneration, and Reprogramming","volume":"14","author":"Miyajima","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jhep.2006.05.002","article-title":"Different types of liver progenitor cells and their niches","volume":"45","author":"Roskams","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1053\/jhep.2001.21900","article-title":"Heterogeneity and plasticity of hepatocyte lineage cells","volume":"33","author":"Sell","year":"2001","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1146\/annurev-physiol-021113-170255","article-title":"Cellular Homeostasis and Repair in the Mammalian Liver","volume":"77","author":"Stanger","year":"2015","journal-title":"Annu. Rev. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1055\/s-2004-815559","article-title":"Overview of Recent Experimental Studies on Liver Stem Cells","volume":"23","author":"Thorgeirsson","year":"2003","journal-title":"Semin. Liver Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1034\/j.1600-0676.2002.01702.x","article-title":"Cell proliferation and renewal of normal hepatocytes and bile duct cells in adult mouse liver","volume":"22","author":"Magami","year":"2002","journal-title":"Liver Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0014-4827(64)90165-X","article-title":"Changes in the replication times and patterns of the liver cell during the life of the rat","volume":"36","author":"Hoffman","year":"1964","journal-title":"Exp. Cell Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/0012-1606(70)90138-7","article-title":"Changes in the distribution of thymidine-3H labeled cells in the growing liver acinus of neonatal rats","volume":"23","author":"LeBouton","year":"1970","journal-title":"Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/jcp.1041290112","article-title":"Dexamethasone and dimethylsulfoxide as distinct regulators of growth and differentiation of cultured suckling rat hepatocytes","volume":"129","author":"Marceau","year":"1986","journal-title":"J. Cell. Physiol."},{"key":"ref_38","first-page":"3145","article-title":"Effect of age on the formation of small-cell colonies in cultures of primary rat hepatocytes","volume":"53","author":"Mitaka","year":"1993","journal-title":"Cancer Res."},{"key":"ref_39","first-page":"28","article-title":"Cellular proliferation in the liver","volume":"17","author":"Grisham","year":"1969","journal-title":"Recent Results Cancer Res."},{"key":"ref_40","first-page":"890","article-title":"The liver","volume":"Volume 2","author":"Wright","year":"1984","journal-title":"The Biology of Epithelial Cell Populations"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0074-7696(08)61119-5","article-title":"Regeneration of mammalian liver","volume":"15","author":"Bucher","year":"1963","journal-title":"Int. Rev. Cytol."},{"key":"ref_42","first-page":"1618","article-title":"Reduction of potential for replicative but not unscheduled DNA synthesis in hepatocytes isolated from aged as compared to young rats","volume":"48","author":"Sawada","year":"1988","journal-title":"Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1007\/BF01955375","article-title":"The effect of aging on rat liver regeneration","volume":"38","author":"Schapiro","year":"1982","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_44","first-page":"400","article-title":"Regeneration of liver parenchyma under normal and pathological conditions","volume":"144","author":"Heine","year":"1971","journal-title":"Beitr. Pathol."},{"key":"ref_45","first-page":"659","article-title":"Aging and the liver","volume":"Volume 8","author":"Popper","year":"1986","journal-title":"Progress in Liver Diseases"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/hep.1840130105","article-title":"Multiple cell cycles occur in rat hepatocytes cultured in the presence of nicotinamide and epidermal growth factor","volume":"13","author":"Mitaka","year":"1991","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1089\/ten.2005.11.626","article-title":"Hepatic Organoid Formation in Collagen Sponge of Cells Isolated from Human Liver Tissues","volume":"11","author":"Sugimoto","year":"2005","journal-title":"Tissue Eng."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1006\/bbrc.1995.2289","article-title":"Growth and Maturation of Small Hepatocytes Isolated from Adult Rat Liver","volume":"214","author":"Mitaka","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/hep.510290103","article-title":"Reconstruction of hepatic organoid by rat small hepatocytes and hepatic nonparenchymal cells","volume":"29","author":"Mitaka","year":"1999","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/j.stemcr.2022.05.023","article-title":"Small-molecule inhibitor cocktail promotes the proliferation of pre-existing liver progenitor cells","volume":"17","author":"Fu","year":"2022","journal-title":"Stem Cell Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.stem.2016.10.007","article-title":"Conversion of Terminally Committed Hepatocytes to Culturable Bipotent Progenitor Cells with Regenerative Capacity","volume":"20","author":"Katsuda","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1242\/jcs.01279","article-title":"Small hepatocytes in culture develop polarized transporter expression and differentiation","volume":"117","author":"Inderbitzin","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1002\/stem.2457","article-title":"Liver Progenitors Isolated from Adult Healthy Mouse Liver Efficiently Differentiate to Functional Hepatocytes In Vitro and Repopulate Liver Tissue","volume":"34","author":"Tanimizu","year":"2016","journal-title":"Stem Cells"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000070375","article-title":"Proliferation and Hepatic Differentiation of Adult-Derived Progenitor Cells","volume":"173","author":"Wang","year":"2003","journal-title":"Cells Tissues Organs"},{"key":"ref_55","first-page":"5964","article-title":"Autonomous growth in serum-free medium and production of hepatocellular carcinomas by differentiated hepatocyte lines that overexpress transforming growth factor alpha 1","volume":"54","author":"Wu","year":"1994","journal-title":"Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1016\/S0002-9440(10)65075-4","article-title":"The in vitro differentiating capacity of nonparenchymal epithelial cells derived from adult porcine livers","volume":"156","author":"Kano","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.3727\/096368908787236666","article-title":"Proliferation of Hepatocyte Progenitor Cells Isolated from Adult Human Livers in Serum-Free Medium","volume":"17","author":"Sasaki","year":"2008","journal-title":"Cell Transplant."},{"key":"ref_58","first-page":"1593","article-title":"Growth and differentiation in culture of clonogenic hepatocytes that express both phenotypes of hepatocytes and biliary epithelial cells","volume":"149","author":"Tateno","year":"1996","journal-title":"Am. J. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"46177","DOI":"10.1038\/srep46177","article-title":"Hepatocytic parental progenitor cells of rat small hepatocytes maintain self-renewal capability after long-term culture","volume":"7","author":"Ishii","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/0092-8674(90)90010-C","article-title":"Neonatal bleeding in transgenic mice expressing urokinase-type plasminogen activator","volume":"62","author":"Heckel","year":"1990","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0092-8674(91)90615-6","article-title":"Complete hepatic regeneration after somatic deletion of an albumin-plasminogen activator transgene","volume":"66","author":"Sandgren","year":"1991","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1126\/science.8108734","article-title":"Replacement of Diseased Mouse Liver by Hepatic Cell Transplantation","volume":"263","author":"Rhim","year":"1994","journal-title":"Science"},{"key":"ref_63","first-page":"2298","article-title":"Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice","volume":"7","author":"Grompe","year":"1993","journal-title":"Minerva Anestesiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1101\/gad.7.12a.2285","article-title":"Rescue of mice homozygous for lethal albino deletions: Implications for an animal model for the human liver disease tyrosinemia type 1","volume":"7","author":"Kelsey","year":"1993","journal-title":"Genes Dev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/ng0396-266","article-title":"Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type I","volume":"12","author":"Overturf","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_66","first-page":"1273","article-title":"Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes","volume":"151","author":"Overturf","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1053\/j.gastro.2010.12.003","article-title":"Activin A, p15INK4b Signaling, and Cell Competition Promote Stem\/Progenitor Cell Repopulation of Livers in Aging Rats","volume":"140","author":"Menthena","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_68","first-page":"785","article-title":"Sexual difference in the histochemical characteristics of \u201caltered cell foci\u201d in the liver of aged Fischer 344 rats","volume":"78","author":"Mitaka","year":"1987","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_69","first-page":"413","article-title":"Mosaic pattern of ornithine transcarbamylase expression in spfash mouse liver","volume":"151","author":"Shiojiri","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1073\/pnas.73.5.1693","article-title":"Abnormal ornithine carbamoyltransferase in mice having the sparse-fur mutation","volume":"73","author":"DeMars","year":"1976","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1006\/dbio.1994.1274","article-title":"Fractal Geometry in Rat Chimeras Demonstrates That a Repetitive Cell Division Program May Generate Liver Parenchyma","volume":"165","author":"Khokha","year":"1994","journal-title":"Dev. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/0012-1606(92)90182-G","article-title":"Fractal geometry of mosaic pattern demonstrates liver regeneration is a self-similar process","volume":"151","author":"Ng","year":"1992","journal-title":"Dev. Biol."},{"key":"ref_73","first-page":"160","article-title":"Experiments in transgenic mice show that hepatocytes are the source for postnatal liver growth and do not stream","volume":"22","author":"Kennedy","year":"1995","journal-title":"Hepatology"},{"key":"ref_74","first-page":"896","article-title":"Cell lineage study in the liver using retroviral mediated gene transfer: Evidence against the streaming of hepatocytes in normal liver","volume":"144","author":"Bralet","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1600-0676.1988.tb00972.x","article-title":"The streaming liver II. Hepatocyte life history","volume":"8","author":"Arber","year":"1988","journal-title":"Liver Int."},{"key":"ref_76","first-page":"105","article-title":"Liver stem cells","volume":"7","author":"Sell","year":"1994","journal-title":"Mod. Pathol."},{"key":"ref_77","first-page":"G139","article-title":"The liver as a stem cell and lineage system","volume":"263","author":"Sigal","year":"1992","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1600-0676.1985.tb00252.x","article-title":"The streaming liver","volume":"5","author":"Zajicek","year":"1985","journal-title":"Liver Int."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1083\/jcb.132.6.1133","article-title":"Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF\/SF, EGF and TGF alpha in a chemically defined (HGM) medium","volume":"132","author":"Block","year":"1996","journal-title":"J. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/jcp.1041470316","article-title":"Amino acid-rich medium (Leibovitz L-15) enhances and prolongs proliferation of primary cultured rat hepatocytes in the absence of serum","volume":"147","author":"Mitaka","year":"1991","journal-title":"J. Cell. Physiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/oxfordjournals.aje.a120336","article-title":"THE GROWTH AND MAINTENANCE OF TISSUE\u2013CELL CULTURES IN FREE GAS EXCHANGE WITH THE ATMOSPHERE1","volume":"78","author":"Leibovitz","year":"1963","journal-title":"Am. J. Epidemiology"},{"key":"ref_82","unstructured":"Harris, R.A., and Cornell, N.W. (1983). Isolation, Characterization, and Use of Hepatocytes, Elsevier."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1002\/hep.510260611","article-title":"Exposure of primary rat hepatocytes in long-term DMSO culture to selected transition metals induces hepatocyte proliferation and formation of duct-like structures","volume":"26","author":"Cable","year":"1997","journal-title":"Hepatology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1073\/pnas.82.10.3252","article-title":"Maintenance of differentiated rat hepatocytes in primary culture","volume":"82","author":"Isom","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s005340200096","article-title":"Reconstruction of hepatic organoid by hepatic stem cells","volume":"9","author":"Mitaka","year":"2002","journal-title":"J. Hepato-Biliary-Pancreatic Surg."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/jcb.10274","article-title":"Morphological changes induced by extracellular matrix are correlated with maturation of rat small hepatocytes","volume":"87","author":"Sugimoto","year":"2002","journal-title":"J. Cell. Biochem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0168-8278(02)00069-7","article-title":"Proliferation of rat small hepatocytes after long-term cryopreservation","volume":"37","author":"Ikeda","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1124\/dmd.105.008342","article-title":"Cytochrome P450 Expression of Cultured Rat Small Hepatocytes after Long-Term Cryopreservation","volume":"34","author":"Ooe","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jhep.2006.01.029","article-title":"Expression of CD44 in rat hepatic progenitor cells","volume":"45","author":"Kon","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1136\/mp.52.4.189","article-title":"CD44 cell adhesion molecules","volume":"52","author":"Goodison","year":"1999","journal-title":"Mol. Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/hep.26084","article-title":"Differentiation capacity of hepatic stem\/progenitor cells isolated from D -galactosamine-treated rat livers","volume":"57","author":"Ichinohe","year":"2012","journal-title":"Hepatology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.2353\/ajpath.2009.080338","article-title":"Thy1-Positive Cells Have Bipotential Ability to Differentiate into Hepatocytes and Biliary Epithelial Cells in Galactosamine-Induced Rat Liver Regeneration","volume":"175","author":"Kon","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.yexcr.2004.09.017","article-title":"Stabilin-1 and stabilin-2 are both directed into the early endocytic pathway in hepatic sinusoidal endothelium via interactions with clathrin\/AP-2, independent of ligand binding","volume":"303","author":"Hansen","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_94","first-page":"8079","article-title":"LYVE-1 is not restricted to the lymph vessels: Expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis","volume":"61","author":"Nasser","year":"2001","journal-title":"Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/nprot.2007.118","article-title":"Selective proliferation of rat hepatocyte progenitor cells in serum-free culture","volume":"2","author":"Chen","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6188","DOI":"10.1021\/bi00267a025","article-title":"Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma","volume":"21","author":"Kleinman","year":"1982","journal-title":"Biochemistry"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.matbio.2005.12.001","article-title":"Ligand-binding specificities of laminin-binding integrins: A comprehensive survey of laminin\u2013integrin interactions using recombinant \u03b13\u03b21, \u03b16\u03b21, \u03b17\u03b21 and \u03b16\u03b24 integrins","volume":"25","author":"Nishiuchi","year":"2006","journal-title":"Matrix Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/bs.ctm.2015.07.002","article-title":"Molecular basis of laminin-integrin interactions","volume":"76","author":"Yamada","year":"2015","journal-title":"Curr. Top. Membr."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.yexcr.2005.01.005","article-title":"Transient expression of laminin \u03b11 chain in regenerating murine liver: Restricted localization of laminin chains and nidogen-1","volume":"305","author":"Kikkawa","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/hep4.1442","article-title":"Self-Renewal Capability of Hepatocytic Parental Progenitor Cells Derived From Adult Rat Liver Is Maintained Long Term When Cultured on Laminin 111 in Serum-Free Medium","volume":"4","author":"Kino","year":"2019","journal-title":"Hepatol. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"28586","DOI":"10.1074\/jbc.M112.350488","article-title":"\u03b11- and \u03b15-containing Laminins Regulate the Development of Bile Ducts via \u03b21 Integrin Signals","volume":"287","author":"Tanimizu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.stemcr.2013.08.006","article-title":"Long-Term Self-Renewal of Human ES\/iPS-Derived Hepatoblast-like Cells on Human Laminin 111-Coated Dishes","volume":"1","author":"Takayama","year":"2013","journal-title":"Stem Cell Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nbt.1620","article-title":"Long-term self-renewal of human pluripotent stem cells on human recombinant laminin-511","volume":"28","author":"Rodin","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1083\/jcb.200108066","article-title":"Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver","volume":"156","author":"Suzuki","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1242\/jcs.00388","article-title":"Isolation of hepatoblasts based on the expression of Dlk\/Pref-1","volume":"116","author":"Tanimizu","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1242\/jcs.01572","article-title":"Long-term culture of hepatic progenitors derived from mouse Dlk+ hepatoblasts","volume":"117","author":"Tanimizu","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"12132","DOI":"10.1073\/pnas.97.22.12132","article-title":"Clonogenic hepatoblasts, common precursors for hepatocytic and biliary lineages, are lacking classical major histocompatibility complex class I antigen","volume":"97","author":"Kubota","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.cell.2015.07.026","article-title":"Hybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer","volume":"162","author":"Shalapour","year":"2015","journal-title":"Cell"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"13369","DOI":"10.1038\/ncomms13369","article-title":"Mfsd2a+ hepatocytes repopulate the liver during injury and regeneration","volume":"7","author":"Pu","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/nature14863","article-title":"Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver","volume":"524","author":"Wang","year":"2015","journal-title":"Nature"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1002\/hep.30563","article-title":"Tissue Repair in the Mouse Liver Following Acute Carbon Tetrachloride Depends on Injury-Induced Wnt\/\u03b2-Catenin Signaling","volume":"69","author":"Zhao","year":"2019","journal-title":"Hepatology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature11826","article-title":"In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration","volume":"494","author":"Huch","year":"2013","journal-title":"Nature"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/s41586-018-0004-7","article-title":"Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury","volume":"556","author":"Lin","year":"2018","journal-title":"Nature"},{"key":"ref_114","first-page":"467","article-title":"The RSPO\u2013LGR4\/5\u2013ZNRF3\/RNF43 module controls liver zonation and size","volume":"18","author":"Orsini","year":"2016","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"19530","DOI":"10.1073\/pnas.1908099116","article-title":"Lgr5+ pericentral hepatocytes are self-maintained in normal liver regeneration and susceptible to hepatocarcinogenesis","volume":"116","author":"Ang","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1126\/science.abc4346","article-title":"Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair","volume":"371","author":"He","year":"2021","journal-title":"Science"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.stem.2019.11.014","article-title":"In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration","volume":"26","author":"Matsumoto","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.jhep.2023.01.009","article-title":"Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration","volume":"78","author":"May","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/hep.27917","article-title":"Paradoxes in studies of liver regeneration: Relevance of the parable of the blind men and the elephant","volume":"62","author":"Reid","year":"2015","journal-title":"Hepatology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.stem.2019.10.011","article-title":"AXIN2+ Pericentral Hepatocytes Have Limited Contributions to Liver Homeostasis and Regeneration","volume":"26","author":"Sun","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1126\/science.abb1625","article-title":"Liver homeostasis is maintained by midlobular zone 2 hepatocytes","volume":"371","author":"Wei","year":"2021","journal-title":"Science"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1046\/j.1432-0436.1995.5910035.x","article-title":"Evidence for a terminal differentiation process in the liver","volume":"59","author":"Sigal","year":"1995","journal-title":"Differentiation"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/hep.510310113","article-title":"Heterogeneity of growth potential of adult rat hepatocytesin vitro","volume":"31","author":"Tateno","year":"2000","journal-title":"Hepatology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.bbrc.2006.02.076","article-title":"Multiplicative mononuclear small hepatocytes in adult rat liver: Their isolation as a homogeneous population and localization to periportal zone","volume":"342","author":"Asahina","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1002\/hep.22516","article-title":"The stem cell niche of human livers: Symmetry between development and regeneration","volume":"48","author":"Zhang","year":"2008","journal-title":"Hepatology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00428-011-1048-3","article-title":"Ductal plates in hepatic ductular reactions. Hypothesis and implications. I. Types of ductular reaction reconsidered","volume":"458","author":"Desmet","year":"2011","journal-title":"Virchows Arch."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1002\/hep.21569","article-title":"Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell\u2013mediated liver regeneration","volume":"45","author":"Jelnes","year":"2007","journal-title":"Hepatology"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S1084952102001258","article-title":"Hepatic progenitor cells in human liver diseases","volume":"13","author":"Libbrecht","year":"2002","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S0168-8278(98)80065-2","article-title":"Hepatic OV-6 expression in human liver disease and rat experiments: Evidence for hepatic progenitor cells in man","volume":"29","author":"Roskams","year":"1998","journal-title":"J. Hepatol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1053\/jhep.2001.24453","article-title":"Expression of anti-OV6 antibody and anti-N-CAM antibody along the biliary line of normal and diseased human livers","volume":"33","author":"Heuvel","year":"2001","journal-title":"Hepatology"},{"key":"ref_131","first-page":"124","article-title":"Human liver regeneration following massive hepatic necrosis: Two distinct patterns","volume":"35","author":"Nagy","year":"2019","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1002\/hep.24613","article-title":"Ductular reactions in human liver: Diversity at the interface","volume":"54","author":"Gouw","year":"2011","journal-title":"Hepatology"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1097\/01.LAB.0000092229.93203.57","article-title":"A Crucial Role of Hepatocyte Nuclear Factor-4 Expression in the Differentiation of Human Ductular Hepatocytes","volume":"83","author":"Hakoda","year":"2003","journal-title":"Lab. Investig."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1600-0676.1993.tb00617.x","article-title":"Cytokeratins and the liver","volume":"13","author":"Eyken","year":"2008","journal-title":"Liver Int."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1053\/gast.1996.v110.pm8613008","article-title":"Liver damage in the rat induces hepatocyte stem cells from biliary epithelial cells","volume":"110","author":"Alison","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1002\/hep.25713","article-title":"Structural analysis of oval-cell-mediated liver regeneration in rats","volume":"56","author":"Papp","year":"2012","journal-title":"Hepatology"},{"key":"ref_137","first-page":"5469","article-title":"In situ hybridization studies on expression of albumin and a-fetoprotein during the early stage of neoplastic transformation in rat liver","volume":"47","author":"Evarts","year":"1987","journal-title":"Cancer Res."},{"key":"ref_138","first-page":"1114","article-title":"Cell behavior in the acetylaminofluorene-treated regenerating rat liver. Light. and electron microscopic observations","volume":"145","author":"Sarraf","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3181\/00379727-129-33301","article-title":"Sulfotransferase Activation of N-Hydroxy-2-acetylaminofluorene in Rodent Livers Susceptible and Resistant to this Carcinogen","volume":"129","author":"DeBaun","year":"1968","journal-title":"Exp. Biol. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1126\/science.284.5417.1168","article-title":"Bone Marrow as a Potential Source of Hepatic Oval Cells","volume":"284","author":"Petersen","year":"1999","journal-title":"Science"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.2353\/ajpath.2007.070273","article-title":"Thy-1 Is Expressed in Hepatic Myofibroblasts and Not Oval Cells in Stem Cell-Mediated Liver Regeneration","volume":"171","author":"Jelnes","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s00441-007-0437-z","article-title":"Thy-1 is an in vivo and in vitro marker of liver myofibroblasts","volume":"329","author":"Dudas","year":"2007","journal-title":"Cell Tissue Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1042\/bj1660455","article-title":"Studies on rat liver plasma membrane. Altered protein and phospholipid metabolism after injection of d-galactosamine","volume":"166","author":"Bachmann","year":"1977","journal-title":"Biochem. J."},{"key":"ref_144","first-page":"78","article-title":"Galactosamine hepatitis: Key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death","volume":"71","author":"Decker","year":"1974","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/0014-4800(70)90075-4","article-title":"Liver restitution after acute galactosamine hepatitis: Autoradiographic and biochemical studies in rats","volume":"12","author":"Lesch","year":"1970","journal-title":"Exp. Mol. Pathol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0014-4800(70)90050-X","article-title":"Ultrastructural features in galactosamine-induced hepatitis","volume":"12","author":"Medline","year":"1970","journal-title":"Exp. Mol. Pathol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3727\/096368911X580626","article-title":"Growth Ability and Repopulation Efficiency of Transplanted Hepatic Stem Cells, Progenitor Cells, and Mature Hepatocytes in Retrorsine-Treated Rat Livers","volume":"21","author":"Ichinohe","year":"2012","journal-title":"Cell Transplant."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1053\/jhep.2003.50007","article-title":"Characterization of cell types during rat liver development","volume":"37","author":"Fiegel","year":"2003","journal-title":"Hepatology"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1053\/jhep.2003.50448","article-title":"Establishment, characterization, and long-term maintenance of cultures of human fetal hepatocytes","volume":"38","year":"2003","journal-title":"Hepatology"},{"key":"ref_150","first-page":"G45","article-title":"Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1","volume":"291","author":"Masson","year":"2006","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1002\/hep.21775","article-title":"Comparison of hepatic properties and transplantation of Thy-1+ and Thy-1\u2212 cells isolated from embryonic day 14 rat fetal liver","volume":"46","author":"Oertel","year":"2007","journal-title":"Hepatology"},{"key":"ref_152","first-page":"429","article-title":"The toxic actions of pyrrolizidine (senecio) alkaloids","volume":"42","author":"McLean","year":"1970","journal-title":"Pharmacol. Rev."},{"key":"ref_153","first-page":"5825","article-title":"Liver regeneration and a-fetoprotein messenger RNA expression in the retrorsine model for hepatocyte transplantation","volume":"58","author":"Dabeva","year":"1998","journal-title":"Cancer Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/carcin\/16.1.139","article-title":"Transplantation of normal hepatocytes modulates the development of chronic liver lesions induced by a pyrrolizidine alkaloid, lasiocarpinet","volume":"16","author":"Laconi","year":"1995","journal-title":"Carcinog."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0002-9440(10)65574-5","article-title":"Long-Term, Near-Total Liver Replacement by Transplantation of Isolated Hepatocytes in Rats Treated with Retrorsine","volume":"153","author":"Laconi","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1002\/hep.510300418","article-title":"Role of thyroid hormone in stimulating liver repopulation in the rat by transplanted hepatocytes","volume":"30","author":"Oren","year":"1999","journal-title":"Hepatology"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1053\/jhep.2000.9144","article-title":"Bax-mediated apoptosis in the livers of rats after partial hepatectomy in the retrorsine model of hepatocellular injury","volume":"32","author":"Gordon","year":"2000","journal-title":"Hepatology"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/stem.2548","article-title":"Transplantation of Thy1+ Cells Accelerates Liver Regeneration by Enhancing the Growth of Small Hepatocyte-Like Progenitor Cells via IL17RB Signaling","volume":"35","author":"Ichinohe","year":"2016","journal-title":"Stem Cells"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jhep.2007.11.002","article-title":"Cells of origin of small hepatocyte-like progenitor cells in the retrorsine model of rat liver injury and regeneration","volume":"48","author":"Best","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.jhep.2007.11.001","article-title":"Origin of small hepatocyte-like progenitor in retrorsine-treated rats","volume":"48","author":"Pichard","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/hep.26104","article-title":"Contribution of mature hepatocytes to small hepatocyte-like progenitor cells in retrorsine-exposed rats with chimeric livers","volume":"57","author":"Chen","year":"2012","journal-title":"Hepatology"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/hep.21018","article-title":"The sources of parenchymal regeneration after chronic hepatocellular liver injury in mice","volume":"43","author":"Vig","year":"2006","journal-title":"Hepatology"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jhep.2004.07.029","article-title":"Mature hepatocytes are the source of small hepatocyte-like progenitor cells in the retrorsine model of liver injury","volume":"41","author":"Avril","year":"2004","journal-title":"J. Hepatol."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Pichard, V., Aubert, D., and Ferry, N. (2009). Direct In Vivo Cell Lineage Analysis in the Retrorsine and 2AAF Models of Liver Injury after Genetic Labeling in Adult and Newborn Rats. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007267"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/hep.20685","article-title":"Cellular responses in experimental liver injury: Possible cellular origins of regenerative stem-like progenitor cells","volume":"41","author":"Coleman","year":"2005","journal-title":"Hepatology"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S0002-9440(10)64591-9","article-title":"Temporal Analysis of Hepatocyte Differentiation by Small Hepatocyte-Like Progenitor Cells during Liver Regeneration in Retrorsine-Exposed Rats","volume":"157","author":"Gordon","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"4871","DOI":"10.1021\/bi00437a052","article-title":"Occurrence and inducibility of cytochrome P 450IIIA in maternal and fetal rats during prenatal development","volume":"28","author":"Hulla","year":"1989","journal-title":"Biochemistry"},{"key":"ref_168","first-page":"462","article-title":"Developmental expression and in situ localization of the phenobarbital-inducible rat hepatic mRNAs for cytochromes CYP2B1, CYP2B2, CYP2C6, and CYP 3A1","volume":"38","author":"Omiecinski","year":"1990","journal-title":"Mol. Pharmacol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/(SICI)1097-0029(19971201)39:5<424::AID-JEMT5>3.0.CO;2-G","article-title":"Expression and inducibility of P450 enzymes during liver ontogeny","volume":"39","author":"Rich","year":"1997","journal-title":"Microsc. Res. Tech."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1006\/exmp.2000.2308","article-title":"Induction of Cytochrome P450 Enzymes in the Livers of Rats Treated with the Pyrrolizidine Alkaloid Retrorsine","volume":"69","author":"Gordon","year":"2000","journal-title":"Exp. Mol. Pathol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1186\/s13287-021-02387-6","article-title":"Extracellular vesicles containing miR-146a-5p secreted by bone marrow mesenchymal cells activate hepatocytic progenitors in regenerating rat livers","volume":"12","author":"Ichinohe","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1097\/00007890-200204270-00008","article-title":"Isolation, short-term culture, and transplantation of small hepatocyte-like progenitor cells from retrorsine-exposed rats1","volume":"73","author":"Gordon","year":"2002","journal-title":"Transplantation"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH700>3.0.CO;2-5","article-title":"Deep intralobular extension of human hepatic \u2018progenitor cells\u2019 correlates with parenchymal inflammation in chronic viral hepatitis: Can \u2018progenitor cells\u2019 migrate?","volume":"192","author":"Libbrecht","year":"2000","journal-title":"J. Pathol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0002-9440(10)65299-6","article-title":"Oval Cell Numbers in Human Chronic Liver Diseases Are Directly Related to Disease Severity","volume":"154","author":"Lowes","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0002-9440(10)63489-X","article-title":"Oxidative Stress and Oval Cell Accumulation in Mice and Humans with Alcoholic and Nonalcoholic Fatty Liver Disease","volume":"163","author":"Roskams","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1002\/hep.1840080619","article-title":"The development of the intrahepatic bile ducts in man: A keratin-immunohistochemical study","volume":"8","author":"Sciot","year":"1988","journal-title":"Hepatology"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3389\/fphys.2015.00178","article-title":"Two sides of one coin: Massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure","volume":"6","author":"Weng","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/PAP.0000000000000112","article-title":"The Pathology of Acute Liver Failure","volume":"23","author":"Lefkowitch","year":"2016","journal-title":"Adv. Anat. Pathol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1111\/j.1478-3231.2006.01377.x","article-title":"Liver regeneration in acute severe liver impairment: A clinicopathological correlation study","volume":"26","author":"Katoonizadeh","year":"2006","journal-title":"Liver Int."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/modpathol.3880029","article-title":"Sequential Observation of Liver Cell Regeneration after Massive Hepatic Necrosis in Auxiliary Partial Orthotopic Liver Transplantation","volume":"13","author":"Fujita","year":"2000","journal-title":"Mod. Pathol."},{"key":"ref_181","first-page":"1119","article-title":"Auxiliary liver transplantation: Regeneration of the native liver and outcome in 30 patients with fulminant hepatic failure-a multicenter European study","volume":"23","author":"Boudjema","year":"1996","journal-title":"Hepatology"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1002\/lt.21568","article-title":"Auxiliary transplantation for acute liver failure: Histopathological study of native liver regeneration","volume":"14","author":"Quaglia","year":"2008","journal-title":"Liver Transplant."},{"key":"ref_183","first-page":"70","article-title":"Phenotypic characterization of hepatic proliferation: Antigenic expression by proliferating epithelial cells in fetal liver, massive hepatic necrosis, and nodular transformation of the liver","volume":"110","author":"Gerber","year":"1983","journal-title":"Am. J. Pathol."},{"key":"ref_184","first-page":"259","article-title":"Ductular reaction its diagnostic significance","volume":"15","author":"Roskams","year":"1998","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_185","first-page":"433","article-title":"Ductular hepatocytes","volume":"10","author":"Sirica","year":"1995","journal-title":"Histol. Histopathol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1002\/hep.510300614","article-title":"The canals of hering and hepatic stem cells in humans","volume":"30","author":"Theise","year":"1999","journal-title":"Hepatology"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1053\/j.gastro.2004.09.076","article-title":"Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection","volume":"128","author":"Marshall","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1096\/fj.01-0977com","article-title":"Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis","volume":"16","author":"Wiemann","year":"2002","journal-title":"FASEB J."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/0016-5085(94)90824-9","article-title":"Clonal analysis of regenerative nodules in hepatitis C virus-induced liver cirrhosis","volume":"107","author":"Aihara","year":"1994","journal-title":"Gastroenterology"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1002\/hep.23483","article-title":"The histogenesis of regenerative nodules in human liver cirrhosis","volume":"51","author":"Lin","year":"2009","journal-title":"Hepatology"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/jcp.1041570305","article-title":"Effects of mitogens and co-mitogens on the formation of small-cell colonies in primary cultures of rat hepatocytes","volume":"157","author":"Mitaka","year":"1993","journal-title":"J. Cell. Physiol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1006\/excr.1998.4304","article-title":"Pleiotrophin as a Swiss 3T3 Cell-Derived Potent Mitogen for Adult Rat Hepatocytes","volume":"246","author":"Sato","year":"1999","journal-title":"Exp. Cell Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.yexmp.2009.10.009","article-title":"Cytokine-dependent activation of small hepatocyte-like progenitor cells in retrorsine-induced rat liver injury","volume":"88","author":"Best","year":"2010","journal-title":"Exp. Mol. Pathol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s13287-023-03346-z","article-title":"CINC-2 and miR-199a-5p in EVs secreted by transplanted Thy1+ cells activate hepatocytic progenitor cell growth in rat liver regeneration","volume":"14","author":"Ichinohe","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1247\/csf.20.167","article-title":"TGF-.BETA. Completely Blocks the Formation of Small-Cell Colonies: Effects of Mito-inhibitory Factors on the Proliferation of Primary Cultured Rat Hepatocytes","volume":"20","author":"Mitaka","year":"1995","journal-title":"Cell Struct. Funct."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1096\/fasebj.4.2.2404819","article-title":"Liver regeneration: Molecular mechanisms of growth control","volume":"4","author":"Michalopoulos","year":"1990","journal-title":"FASEB J."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1002\/jcp.22971","article-title":"Proliferation of rat small hepatocytes requires follistatin expression","volume":"227","author":"Ooe","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"ref_198","first-page":"104","article-title":"Hepatocyte proliferation induced in rats by lead nitrate is suppressed by several tumor necrosis factor alpha inhibitors","volume":"23","author":"Kubo","year":"1996","journal-title":"Hepatology"},{"key":"ref_199","first-page":"951","article-title":"Dexamethasone inhibits induction of liver tumor necrosis factor-alpha mRNA and liver growth induced by lead nitrate and ethylene dibromide","volume":"145","author":"Columbano","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/hep.510280220","article-title":"Dexamethasone inhibits the proliferation of hepatocytes and oval cells but not bile duct cells in rat liver","volume":"28","author":"Nagy","year":"1998","journal-title":"Hepatology"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1002\/hep.1840200413","article-title":"Induction of apoptosis in the murine liver with recombinant human activin a","volume":"20","author":"Hully","year":"1994","journal-title":"Hepatology"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1053\/jhep.2001.29132","article-title":"Transforming growth factor \u03b2 and activin tonically inhibit DNA synthesis in the rat liver","volume":"34","author":"Ichikawa","year":"2001","journal-title":"Hepatology"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1053\/he.2000.6100","article-title":"The role of activin and transforming growth factor-\u03b2 in the regulation of organ mass in the rat liver","volume":"31","author":"Kogure","year":"2000","journal-title":"Hepatology"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1053\/jhep.2003.50483","article-title":"Adenovirus-mediated overexpression of follistatin enlarges intact liver of adult rats","volume":"38","author":"Takabe","year":"2003","journal-title":"Hepatology"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1172\/JCI116727","article-title":"Activin A: An autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes","volume":"92","author":"Yasuda","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_206","first-page":"123","article-title":"The activin axis in liver biology and disease","volume":"613","author":"Vejda","year":"2006","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/0016-5085(95)90212-0","article-title":"A single intraportal administration of follistatin accelerates liver regeneration in partially hepatectomized rats","volume":"108","author":"Kogure","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1210\/en.2002-0203","article-title":"Differential Binding and Neutralization of Activins A and B by Follistatin and Follistatin Like-3 (FSTL-3\/FSRP\/FLRG)","volume":"144","author":"Schneyer","year":"2003","journal-title":"Endocrinology"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/hep.1840180219","article-title":"Activin induces cell death in hepatocytes in vivo and in vitro","volume":"18","author":"Schwall","year":"1993","journal-title":"Hepatology"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/hed.21732","article-title":"Resistance to apoptosis-inducing stimuli in CD44+ head and neck squamous cell carcinoma cells","volume":"34","author":"Chikamatsu","year":"2011","journal-title":"Head Neck"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/nrc3023","article-title":"CD44: Can a cancer-initiating cell profit from an abundantly expressed molecule?","volume":"11","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.bbrc.2005.01.129","article-title":"Hepatic progenitor cell resistance to TGF-\u03b21\u2019s proliferative and apoptotic effects","volume":"329","author":"Clark","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/hep.22743","article-title":"CD133+ liver cancer stem cells from methionine adenosyl transferase 1A-deficient mice demonstrate resistance to transforming growth factor (TGF)-\u03b2-induced apoptosis","volume":"49","author":"Ding","year":"2008","journal-title":"Hepatology"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.cub.2012.05.016","article-title":"Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration","volume":"22","author":"Miyaoka","year":"2012","journal-title":"Curr. Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/23\/2718\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:31:31Z","timestamp":1760131891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/23\/2718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,27]]},"references-count":214,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["cells12232718"],"URL":"https:\/\/doi.org\/10.3390\/cells12232718","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,27]]}}}