Understanding the marvels behind liver regeneration

Tissue regeneration is a process by which the remaining cells of an injured organ regrow to offset the missed cells. This field is relatively a new discipline that has been a focus of intense research by clinicians, surgeons, and scientists for decades. It constitutes the cornerstone of tissue engineering, creation of artificial organs, and generation and utilization of therapeutic stem cells to undergo transformation to different types of mature cells. Many medical experts, scientists, biologists, and bioengineers have dedicated their efforts to deeply comprehend the process of liver regeneration, striving for harnessing it to invent new therapies for liver failure. Liver regeneration after partial hepatectomy in rodents has been extensively studied by researchers for many years. It is divided into three important distinctive phases including (a) Initiation or priming phase which includes an overexpression of specific genes to prepare the liver cells for replication, (b) Proliferation phase in which the liver cells undergo a series of cycles of cell division and expansion and finally, (c) termination phase which acts as brake to stop the regenerative process and prevent the liver tissue overgrowth. These events are well controlled by cytokines, growth factors, and signaling pathways. In this review, we describe the function, embryology, and anatomy of human liver, discuss the molecular basis of liver regeneration, elucidate the hepatocyte and cholangiocyte lineages mediating this process, explain the role of hepatic progenitor cells and elaborate the developmental signaling pathways and regulatory molecules required to procure a complete restoration of hepatic lobule.

[1]  S. Nyberg,et al.  Hormonal Contribution to Liver Regeneration , 2020, Mayo Clinic proceedings. Innovations, quality & outcomes.

[2]  G. Van den Berghe,et al.  Endoplasmic reticulum stress actively suppresses hepatic molecular identity in damaged liver , 2020, Molecular systems biology.

[3]  A. Mehrabi,et al.  Markers of liver regeneration—the role of growth factors and cytokines: a systematic review , 2020, BMC Surgery.

[4]  N. Choijookhuu,et al.  The Effect of Estrogen on Hepatic Fat Accumulation during Early Phase of Liver Regeneration after Partial Hepatectomy in Rats , 2019, Acta histochemica et cytochemica.

[5]  S. Ferber,et al.  Liver to Pancreas Transdifferentiation , 2019, Current Diabetes Reports.

[6]  W. Kremers,et al.  Randomized Trial of Spheroid Reservoir Bioartificial Liver in Porcine Model of Posthepatectomy Liver Failure , 2018, Hepatology.

[7]  H. Gilgenkrantz,et al.  Understanding Liver Regeneration: From Mechanisms to Regenerative Medicine. , 2018, The American journal of pathology.

[8]  Jacquelyn O. Russell,et al.  Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology. , 2018, Annual review of pathology.

[9]  B. Petersen,et al.  Hepatic progenitor cell activation in liver repair. , 2017, Liver research.

[10]  Ping Chen,et al.  Proliferation‑inhibiting pathways in liver regeneration (Review). , 2017, Molecular medicine reports.

[11]  K. Cadigan Faculty of 1000 evaluation for Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. , 2017 .

[12]  K. N. Yarygin,et al.  Cellular Mechanisms of Liver Regeneration and Cell-Based Therapies of Liver Diseases , 2017, BioMed research international.

[13]  Mikin V Patel,et al.  Assessing Intra-arterial Complications of Planning and Treatment Angiograms for Y-90 Radioembolization , 2017, CardioVascular and Interventional Radiology.

[14]  M. Jeschke,et al.  Cellular and Molecular Cascades during Liver Regeneration , 2016 .

[15]  Fan Wang,et al.  Notch Signaling Coordinates Progenitor Cell-Mediated Biliary Regeneration Following Partial Hepatectomy , 2016, Scientific Reports.

[16]  S. Kaur,et al.  Hepatic Progenitor Cells in Action: Liver Regeneration or Fibrosis? , 2015, The American journal of pathology.

[17]  R. Nusse,et al.  Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver , 2015, Nature.

[18]  A. Diehl,et al.  Mouse Models of Diet-Induced Nonalcoholic Steatohepatitis Reproduce the Heterogeneity of the Human Disease , 2015, PloS one.

[19]  A. Canbay,et al.  Role of liver progenitors in liver regeneration. , 2015, Hepatobiliary surgery and nutrition.

[20]  M. Strazzabosco,et al.  Emerging roles of Notch signaling in liver disease , 2015, Hepatology.

[21]  F. Anania,et al.  Antagonistic interaction between Wnt and Notch activity modulates the regenerative capacity of a zebrafish fibrotic liver model , 2014, Hepatology.

[22]  R. Nusse,et al.  An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control , 2014, Science.

[23]  S. Nyberg,et al.  Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease. , 2014, Stem cell research.

[24]  A. Miyajima,et al.  Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. , 2014, Cell stem cell.

[25]  H. Poustchi,et al.  Adult Hepatic Progenitor Cell Niche: How it affects the Progenitor Cell Fate , 2014, Middle East journal of digestive diseases.

[26]  D. Stainier,et al.  Extensive conversion of hepatic biliary epithelial cells to hepatocytes after near total loss of hepatocytes in zebrafish. , 2014, Gastroenterology.

[27]  Huiqiang Lu,et al.  Regeneration of liver after extreme hepatocyte loss occurs mainly via biliary transdifferentiation in zebrafish. , 2014, Gastroenterology.

[28]  R. Fiorotto,et al.  Notch signalling beyond liver development: emerging concepts in liver repair and oncogenesis. , 2013, Clinics and research in hepatology and gastroenterology.

[29]  Hamdy Sliem,et al.  Hepatic Embryonic Development and Anomalies of the Liver , 2013 .

[30]  Domenico Ribatti,et al.  "Sprouting angiogenesis", a reappraisal. , 2012, Developmental biology.

[31]  I. Leclercq,et al.  Liver progenitor cells yield functional hepatocytes in response to chronic liver injury in mice. , 2012, Gastroenterology.

[32]  L. Greenbaum,et al.  The role of paracrine signals during liver regeneration , 2012, Hepatology.

[33]  H. Gilgenkrantz,et al.  EGFR: A Master Piece in G1/S Phase Transition of Liver Regeneration , 2012, International journal of hepatology.

[34]  T. Shen,et al.  The role of Cdc25A in the regulation of cell proliferation and apoptosis. , 2012, Anti-cancer agents in medicinal chemistry.

[35]  Ke-shu Xu,et al.  Tubulogenesis during blood vessel formation. , 2011, Seminars in cell & developmental biology.

[36]  B. Lemmers,et al.  Cyclin A2 Mutagenesis Analysis: A New Insight into CDK Activation and Cellular Localization Requirements , 2011, PloS one.

[37]  Yunfang Wang,et al.  Human hepatic stem cell and maturational liver lineage biology , 2011, Hepatology.

[38]  A. Miyajima,et al.  Liver stem/progenitor cells: their characteristics and regulatory mechanisms. , 2011, Journal of biochemistry.

[39]  T. Roskams,et al.  Hepatic progenitor cells: an update. , 2010, Clinics in liver disease.

[40]  S. Werner,et al.  Regulation of liver regeneration by growth factors and cytokines , 2010, EMBO molecular medicine.

[41]  J. Olynyk,et al.  Tumor necrosis factor–like weak inducer of apoptosis is a mitogen for liver progenitor cells , 2010, Hepatology.

[42]  A. Franchitto,et al.  New insights into liver stem cells. , 2009, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[43]  M. A. Bosch,et al.  Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis , 2009, European Radiology.

[44]  K. Dou,et al.  Disruption of the transcription factor recombination signal‐binding protein‐Jκ (RBP‐J) leads to veno‐occlusive disease and interfered liver regeneration in mice , 2009, Hepatology.

[45]  P. Gartside,et al.  Bile duct changes in alcoholic liver disease , 2008 .

[46]  A F Karamysheva,et al.  Mechanisms of angiogenesis , 2008, Biochemistry (Moscow).

[47]  L. Zon,et al.  APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development. , 2008, Developmental biology.

[48]  B. Gabrielli,et al.  Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events , 2008, Oncogene.

[49]  J. I. Izpisúa Belmonte,et al.  Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression , 2008, Development.

[50]  B. Cieply,et al.  β‐Catenin deletion in hepatoblasts disrupts hepatic morphogenesis and survival during mouse development , 2008, Hepatology.

[51]  P. Henriet,et al.  Role of metalloproteinases at the onset of liver development , 2008, Development, growth & differentiation.

[52]  B. Mccright,et al.  Notch Signaling Regulates Bile Duct Morphogenesis in Mice , 2008, PloS one.

[53]  N. Hastie,et al.  Wt1 and retinoic acid signaling are essential for stellate cell development and liver morphogenesis. , 2007, Developmental biology.

[54]  D. Rickman,et al.  Stabilization of β‐catenin affects mouse embryonic liver growth and hepatoblast fate , 2007, Hepatology.

[55]  G. Rousseau,et al.  The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration. , 2007, Developmental biology.

[56]  George K. Michalopoulos Liver regeneration , 2007, Journal of cellular physiology.

[57]  S. Bellusci,et al.  Fibroblast growth factor 10 is critical for liver growth during embryogenesis and controls hepatoblast survival via β‐catenin activation , 2007 .

[58]  Mignon A. Keaton Review of "The Cell Cycle: Principles of Control" by David O. Morgan , 2007, Cell Division.

[59]  Aarati R. Ranade,et al.  Robust expansion of human hepatocytes in Fah−/−/Rag2−/−/Il2rg−/− mice , 2007, Nature Biotechnology.

[60]  M. Kremer,et al.  Impaired liver regeneration and increased oval cell numbers following T cell–mediated hepatitis , 2007, Hepatology.

[61]  A. Zorn,et al.  Repression of Wnt/β-catenin signaling in the anterior endoderm is essential for liver and pancreas development , 2007, Development.

[62]  F. Gaunitz,et al.  Hepatocellular expression of glutamine synthetase: an indicator of morphogen actions as master regulators of zonation in adult liver. , 2007, Progress in histochemistry and cytochemistry.

[63]  H. Nishina,et al.  Liver development and regeneration: From laboratory study to clinical therapy , 2007, Development, growth & differentiation.

[64]  K. Kaestner,et al.  Bile duct proliferation in liver‐specific Jag1 conditional knockout mice: Effects of gene dosage , 2007, Hepatology.

[65]  M. Tomizawa,et al.  Suppression of C/EBPα expression in periportal hepatoblasts may stimulate biliary cell differentiation through increased Hnf6 and Hnf1b expression , 2006, Development.

[66]  K. Kaestner,et al.  An FGF response pathway that mediates hepatic gene induction in embryonic endoderm cells. , 2006, Developmental cell.

[67]  F. Tronche,et al.  Plasticity and expanding complexity of the hepatic transcription factor network during liver development. , 2006, Genes & development.

[68]  H. Yonekawa,et al.  Crucial Role of the Small GTPase ARF6 in Hepatic Cord Formation during Liver Development , 2006, Molecular and Cellular Biology.

[69]  I. Krantz,et al.  NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. , 2006, American journal of human genetics.

[70]  Zhenhai Zhang,et al.  HNF factors form a network to regulate liver-enriched genes in zebrafish. , 2006, Developmental biology.

[71]  Michael Boutros,et al.  Secretion of Wnt Ligands Requires Evi, a Conserved Transmembrane Protein , 2006, Cell.

[72]  W. Jochum,et al.  Platelet-Derived Serotonin Mediates Liver Regeneration , 2006, Science.

[73]  N. Fausto,et al.  Liver regeneration , 2006, Hepatology.

[74]  K. Zaret,et al.  Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development. , 2006, Developmental biology.

[75]  F. Lemaigre,et al.  Control of Hepatic Differentiation by Activin/TGFβ Signaling , 2006, Cell cycle.

[76]  M. P. Holloway,et al.  Survivin splice variants regulate the balance between proliferation and cell death , 2005, Oncogene.

[77]  G. Michalopoulos,et al.  Transdifferentiation of rat hepatocytes into biliary cells after bile duct ligation and toxic biliary injury , 2005, Hepatology.

[78]  David C. Lee,et al.  Amphiregulin: an early trigger of liver regeneration in mice. , 2005, Gastroenterology.

[79]  R. Maronpot,et al.  New Insights into Functional Aspects of Liver Morphology , 2005, Toxicologic pathology.

[80]  R. Kageyama,et al.  The role of notch signaling in the development of intrahepatic bile ducts. , 2004, Gastroenterology.

[81]  J. Ando,et al.  Differential regulation of urokinase-type plasminogen activator expression by fluid shear stress in human coronary artery endothelial cells. , 2004, American journal of physiology. Heart and circulatory physiology.

[82]  N. Shiojiri,et al.  Suppression of C/EBP alpha expression in biliary cell differentiation from hepatoblasts during mouse liver development. , 2004, Journal of hepatology.

[83]  A. Zimmermann Regulation of liver regeneration. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[84]  A. Miyajima,et al.  Notch signaling controls hepatoblast differentiation by altering the expression of liver-enriched transcription factors , 2004, Journal of Cell Science.

[85]  A. West,et al.  Nomenclature of the finer branches of the biliary tree: Canals, ductules, and ductular reactions in human livers , 2004, Hepatology.

[86]  D. Palmes,et al.  Animal models of liver regeneration. , 2004, Biomaterials.

[87]  G. Michalopoulos,et al.  Beta-catenin is temporally regulated during normal liver development. , 2004, Gastroenterology.

[88]  N. Theise,et al.  Canals of Hering: recent insights and current knowledge. , 2004, Seminars in liver disease.

[89]  David P. Toczyski,et al.  Securin and B-cyclin/CDK are the only essential targets of the APC , 2003, Nature Cell Biology.

[90]  F. Lemaigre Development of the biliary tract , 2003, Mechanisms of Development.

[91]  C. Deng,et al.  Disruption of Transforming Growth Factor-β Signaling in ELF β-Spectrin-Deficient Mice , 2003, Science.

[92]  G. Oliver,et al.  Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm , 2002, Mechanisms of Development.

[93]  R. Poon,et al.  Cyclin A in cell cycle control and cancer , 2002, Cellular and Molecular Life Sciences CMLS.

[94]  I. Herman,et al.  Mechanisms of normal and tumor-derived angiogenesis. , 2002, American journal of physiology. Cell physiology.

[95]  A. Bell,et al.  Hepatocyte Growth Factor Induces Wnt-independent Nuclear Translocation of β-Catenin after Met-β-Catenin Dissociation in Hepatocytes , 2002 .

[96]  M. Katsuki,et al.  K‐Ras mediates cytokine‐induced formation of E‐cadherin‐based adherens junctions during liver development , 2002, The EMBO journal.

[97]  J. Rozga Hepatocyte proliferation in health and in liver failure. , 2002, Medical science monitor : international medical journal of experimental and clinical research.

[98]  J. Diehl Cycling to Cancer with Cyclin D1 , 2002, Cancer biology & therapy.

[99]  Hans Clevers,et al.  Negative Feedback Loop of Wnt Signaling through Upregulation of Conductin/Axin2 in Colorectal and Liver Tumors , 2002, Molecular and Cellular Biology.

[100]  Esther Jacobowitz Israel Liver disease in children , 2001 .

[101]  R. Poulsom,et al.  Update on hepatic stem cells. , 2001, Liver.

[102]  S. Hubscher,et al.  Notch receptor expression in adult human liver: A possible role in bile duct formation and hepatic neovascularization , 2001, Hepatology.

[103]  J. Rossant,et al.  Liver Organogenesis Promoted by Endothelial Cells Prior to Vascular Function , 2001, Science.

[104]  Z. Kmieć,et al.  Cooperation of Liver Cells in Health and Disease , 2001, Advances in Anatomy Embryology and Cell Biology.

[105]  C. Deng,et al.  Smad Proteins and Hepatocyte Growth Factor Control Parallel Regulatory Pathways That Converge on β1-Integrin To Promote Normal Liver Development , 2001, Molecular and Cellular Biology.

[106]  Alan Wells,et al.  Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor , 2001, The Journal of cell biology.

[107]  W. Jelkmann,et al.  The role of the liver in the production of thrombopoietin compared with erythropoietin. , 2001, European journal of gastroenterology & hepatology.

[108]  G. Ciliberto,et al.  Global changes in interleukin‐6–dependent gene expression patterns in mouse livers after partial hepatectomy , 2001, Hepatology.

[109]  E. Wagner,et al.  Embryonic lethality and fetal liver apoptosis in mice lacking the c‐raf‐1 gene , 2001, The EMBO journal.

[110]  A. Miyajima,et al.  Oncostatin M and hepatocyte growth factor induce hepatic maturation via distinct signaling pathways , 2001, FEBS letters.

[111]  K. Zaret,et al.  Repressive and restrictive mesodermal interactions with gut endoderm: possible relation to Meckel's Diverticulum. , 2000, Development.

[112]  T. Roskams,et al.  Deep intralobular extension of human hepatic ‘progenitor cells’ correlates with parenchymal inflammation in chronic viral hepatitis: can ‘progenitor cells’ migrate? , 2000, The Journal of pathology.

[113]  Daniel A. Pollard,et al.  Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85α , 2000, Nature Genetics.

[114]  S. Thorgeirsson,et al.  Transforming growth factor-beta1 recruits histone deacetylase 1 to a p130 repressor complex in transgenic mice in vivo. , 2000, Cancer research.

[115]  D. Alvaro,et al.  Regulation and deregulation of cholangiocyte proliferation. , 2000, Journal of hepatology.

[116]  Guillermo Oliver,et al.  Hepatocyte migration during liver development requires Prox1 , 2000, Nature Genetics.

[117]  H. Otto,et al.  Contribution of apoptosis and apoptosis-related proteins to the malformation of the primitive intrahepatic biliary system in Meckel syndrome. , 2000, The American journal of pathology.

[118]  D. Stolz,et al.  Cross-talk between Epidermal Growth Factor Receptor and c-Met Signal Pathways in Transformed Cells* , 2000, The Journal of Biological Chemistry.

[119]  S. Todo,et al.  Sequential Observation of Liver Cell Regeneration after Massive Hepatic Necrosis in Auxiliary Partial Orthotopic Liver Transplantation , 2000, Modern Pathology.

[120]  D. Stolz,et al.  Expression and activation of pro‐MMP‐2 and pro‐MMP‐9 during rat liver regeneration , 2000, Hepatology.

[121]  G. Michalopoulos,et al.  Adrenergic stimulation of hepatocyte growth factor expression. , 1999, Biochemical and biophysical research communications.

[122]  D. Stolz,et al.  Growth factor signal transduction immediately after two-thirds partial hepatectomy in the rat. , 1999, Cancer research.

[123]  Frank Hilberg,et al.  Functions of c-Jun in Liver and Heart Development , 1999, The Journal of cell biology.

[124]  K. Zaret,et al.  GATA transcription factors as potentiators of gut endoderm differentiation. , 1998, Development.

[125]  H. Ikeda,et al.  Activated rat stellate cells express c-met and respond to hepatocyte growth factor to enhance transforming growth factor beta1 expression and DNA synthesis. , 1998, Biochemical and biophysical research communications.

[126]  M. Kay,et al.  Hepatocyte growth factor induces hepatocyte proliferation in vivo and allows for efficient retroviral‐mediated gene transfer in mice , 1998, Hepatology.

[127]  P. van Eyken,et al.  Hepatic OV-6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man. , 1998, Journal of hepatology.

[128]  G. Michalopoulos,et al.  Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats , 1998, Hepatology.

[129]  S. Sell,et al.  Immunolocalization of putative human liver progenitor cells in livers from patients with end-stage primary biliary cirrhosis and sclerosing cholangitis using the monoclonal antibody OV-6. , 1998, The American journal of pathology.

[130]  L. Ohlson,et al.  Inhibition of in vivo rat liver regeneration by 2‐acetylaminofluorene affects the regulation of cell cycle‐related proteins , 1998, Hepatology.

[131]  R. Nusse,et al.  Wnt signaling: a common theme in animal development. , 1997, Genes & development.

[132]  Colin C. Collins,et al.  Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1 , 1997, Nature Genetics.

[133]  M. Kanzaki,et al.  Intravenous administration of follistatin: Delivery to the liver and effect on liver regeneration after partial hepatectomy , 1996, Hepatology.

[134]  Jeremy Nathans,et al.  A new member of the frizzled family from Drosophila functions as a Wingless receptor , 1996, Nature.

[135]  G. Michalopoulos,et al.  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 , 1996, The Journal of cell biology.

[136]  G. Michalopoulos,et al.  Collagenase pretreatment and the mitogenic effects of hepatocyte growth factor and transforming growth factor‐α in adult rat liver , 1994, Hepatology.

[137]  R. Schwall,et al.  Activin induces cell death in hepatocytes in vivo and in vitro , 1993, Hepatology.

[138]  A. Logan,et al.  Angiogenesis , 1993, The Lancet.

[139]  D. V. van Thiel,et al.  Hepatocyte growth factor, blood clearance, organ uptake, and biliary excretion in normal and partially hepatectomized rats. , 1993, Laboratory investigation; a journal of technical methods and pathology.

[140]  G. Michalopoulos,et al.  The presence of hepatocyte growth factor in the developing rat. , 1992, Development.

[141]  R. Pepperkok,et al.  Cyclin A is required at two points in the human cell cycle. , 1992, The EMBO journal.

[142]  H. Moses,et al.  Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development , 1991, The Journal of cell biology.

[143]  F. Schaffner Structural and functional aspects of regeneration of human liver , 1991, Digestive Diseases and Sciences.

[144]  R. Coffey,et al.  Type beta transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[145]  G. Michalopoulos,et al.  Norepinephrine modulates the growth‐inhibitory effect of transforming growth factor‐beta in primary rat hepatocyte cultures , 1988, Journal of cellular physiology.

[146]  G. Michalopoulos,et al.  α1‐Adrenergic effects and liver regeneration , 1987 .

[147]  S. Poulsen,et al.  Adrenergic effects on secretion of epidermal growth factor from Brunner's glands. , 1985, Gut.

[148]  G. Michalopoulos,et al.  Induction of DNA synthesis in cultured rat hepatocytes through stimulation of alpha 1 adrenoreceptor by norepinephrine. , 1985, Science.

[149]  E. Medlock,et al.  The liver hemopoietic environment: I. Developing hepatocytes and their role in fetal hemopoiesis , 1983, The Anatomical record.

[150]  G. Weir,et al.  Insulin, glucagon, liver regeneration, and DNA synthesis. , 1976, Metabolism: clinical and experimental.

[151]  T. Starzl,et al.  EFFECTS OF INSULIN, GLUCAGON, AND INSULIN/GLUCAGON INFUSIONS ON LIVER MORPHOLOGY AND CELL DIVISION AFTER COMPLETE PORTACAVAL SHUNT IN DOGS , 1976, The Lancet.

[152]  E. Farber Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3'-methyl-4-dimethylaminoazobenzene. , 1956, Cancer research.

[153]  G. Shiha,et al.  Liver Regeneration: Summary of Involved Cell Types , 2017 .

[154]  Satdarshan P. S. Monga,et al.  Developmental Pathways in Liver Regeneration-I , 2015 .

[155]  U. Apte,et al.  Models to Study Liver Regeneration , 2015 .

[156]  U. Apte,et al.  Mechanisms of Termination of Liver Regeneration , 2015 .

[157]  S. Nyberg,et al.  Liver regeneration. , 2014, Translational research : the journal of laboratory and clinical medicine.

[158]  N. Fausto,et al.  Liver regeneration. , 2012, Journal of hepatology.

[159]  G. Michalopoulos Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. , 2010, The American journal of pathology.

[160]  B. Carr,et al.  Hepatobiliary effects of 90yttrium microsphere therapy for unresectable hepatocellular carcinoma. , 2009, Human pathology.

[161]  A. Libra,et al.  Studying Liver Regeneration by Means of Molecular Biology: How Far We Are in Interpreting the Findings? , 2009, Acta medica.

[162]  S. Bellusci,et al.  Fibroblast growth factor 10 is critical for liver growth during embryogenesis and controls hepatoblast survival via beta-catenin activation. , 2007, Hepatology.

[163]  G. Michalopoulos,et al.  Wnt impacts growth and differentiation in ex vivo liver development. , 2004, Experimental cell research.

[164]  G. Michalopoulos,et al.  HGF-, EGF-, and dexamethasone-induced gene expression patterns during formation of tissue in hepatic organoid cultures. , 2003, Gene expression.

[165]  Jean S. Campbell,et al.  The role of hepatocytes and oval cells in liver regeneration and repopulation , 2003, Mechanisms of Development.

[166]  C. Deng,et al.  Disruption of transforming growth factor-beta signaling in ELF beta-spectrin-deficient mice. , 2003, Science.

[167]  D. Brenner,et al.  Transforming growth factor-beta1 induces hepatocyte apoptosis by a c-Jun independent mechanism. , 2002, Surgery.

[168]  A. Bell,et al.  Hepatocyte growth factor induces Wnt-independent nuclear translocation of beta-catenin after Met-beta-catenin dissociation in hepatocytes. , 2002, Cancer research.

[169]  Z. Kmieć,et al.  Introduction — Morphology of the Liver Lobule , 2001 .

[170]  P. Gartside,et al.  Bile duct changes in alcoholic liver disease. The Veterans Administration Cooperative Study Group. , 1993, Liver.

[171]  J. Short,et al.  Triidothyronine: on its role as a specific hepatomitogen. , 1980, Cytobios.

[172]  R. Anderson,et al.  Experimental pathology of liver: restoration of liver in white rat following partial surgical removal , 1931 .

[173]  M. Milne The histology of liver tissue regeneration , 1909 .