A decade of liver organoids: Advances in disease modeling
Open accessAbstract
Liver organoids are three-dimensional cellular tissue models in which cells interact to form unique structures in culture. During the past 10 years, liver organoids with various cellular compositions, structural features, and functional properties have been described. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. Liver organoid culture platforms have been used in various research fields, from modeling liver diseases to regenerative therapy. This review discusses how liver organoids are used to model disease, including hereditary liver diseases, primary liver cancer, viral hepatitis, and nonalcoholic fatty liver disease. Specifically, we focus on studies that used either of two widely adopted approaches: differentiation from pluripotent stem cells or epithelial organoids cultured from patient tissues. These approaches have enabled the generation of advanced human liver models and, more importantly, the establishment of patient-tailored models for evaluating disease phenotypes and therapeutic responses at the individual level.
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Proteomics can offer a temporal roadmap of cellular differentiation and functional development in organoids.
“By profiling protein expression dynamics, proteomics can offer a temporal roadmap of cellular differentiation and functional development in organoids14–17.”
From Temporal proteomic profiling of iPSC-derived human liver organoids reveals optimal maturation for drug metabolism and toxicology (2026) · cites this paper as [17]
The Introduction and Hereditary Liver Diseases sections discuss organoid differentiation and functional maturity, but do not describe proteomic profiling as a temporal roadmap. Searches for proteomics, protein expression dynamics, and maturation found no passage addressing that claim; page numbers were unavailable in our copy. (LLM, conf=0.73)
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- [1]Trefts E Gannon M Wasserman DH The liver Curr Biol 2017 27 R1147 R1151 29112863 PMC5897118
- [2]Schulze RJ Schott MB Casey CA Tuma PL McNiven MA The cell biology of the hepatocyte: A membrane trafficking machine J Cell Biol 2019 218 2096 2112 31201265 PMC6605791
- [4]Malik R Selden C Hodgson H The role of non-parenchymal cells in liver growth Semin Cell Dev Biol 2002 13 425 431 12468243
- [5]Kumar S Duan Q Wu R Harris EN Su Q Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis Adv Drug Deliv Rev 2021 176 113869 34280515 PMC11792083
- [6]Cheemerla S Balakrishnan M Global epidemiology of chronic liver disease Clin Liver Dis (Hoboken) 2021 17 365 370 34136143 PMC8177826
- [7]Moon AM Singal AG Tapper EB Contemporary epidemiology of chronic liver disease and cirrhosis Clin Gastroenterol Hepatol 2020 18 2650 2666 31401364 PMC7007353
- [8]Yu JH Ma S Organoids as research models for hepatocellular carcinoma Exp Cell Res 2022 411 112987 34942189
- [9]Liu Y Meyer C Xu C Weng H Hellerbrand C ten Dijke P Animal models of chronic liver diseases Am J Physiol Gastrointest Liver Physiol 2013 304 G449 G468 23275613
- [10]Ortiz C Schierwagen R Schaefer L Klein S Trepat X Trebicka J Extracellular matrix remodeling in chronic liver disease Curr Tissue Microenviron Rep 2021 2 41 52 34337431 PMC8300084
- [11]Simian M Bissell MJ Organoids: A historical perspective of thinking in three dimensions J Cell Biol 2017 216 31 40 28031422 PMC5223613
- [12]Corrò C Novellasdemunt L Li VSW A brief history of organoids Am J Physiol Cell Physiol 2020 319 C151 C165 32459504 PMC7468890
- [13]Evans MJ Kaufman MH Establishment in culture of pluripotential cells from mouse embryos Nature 1981 292 154 156 7242681
- [14]Thomson JA Itskovitz-Eldor J Shapiro SS Waknitz MA Swiergiel JJ Marshall VS Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145-1147 Erratum in: Science 1998 282 1827 9804556
- [16]Lancaster MA Renner M Martin CA Wenzel D Bicknell LS Hurles ME Cerebral organoids model human brain development and microcephaly Nature 2013 501 373 379 23995685 PMC3817409
- [17]Dye BR Hill DR Ferguson MA Tsai YH Nagy MS Dyal R In vitro generation of human pluripotent stem cell derived lung organoids Elife 2015 4 e05098 25803487 PMC4370217
- [20]Spence JR Mayhew CN Rankin SA Kuhar MF Vallance JE Tolle K Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro Nature 2011 470 105 109 21151107 PMC3033971
- [21]Breunig M Merkle J Wagner M Melzer MK Barth TFE Engleitner T Modeling plasticity and dysplasia of pancreatic ductal organoids derived from human pluripotent stem cells Cell Stem Cell 2021 28 1105 1124.e19 33915078 PMC8461636
- [22]Mun SJ Ryu JS Lee MO Son YS Oh SJ Cho HS Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids J Hepatol 2019 71 970 985 31299272
- [24]Rowe RG Daley GQ Induced pluripotent stem cells in disease modelling and drug discovery Nat Rev Genet 2019 20 377 388 30737492 PMC6584039
- [25]Li ML Aggeler J Farson DA Hatier C Hassell J Bissell MJ Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells Proc Natl Acad Sci U S A 1987 84 136 140 3467345 PMC304157
- [26]Shannon JM Mason RJ Jennings SD Functional differentiation of alveolar type II epithelial cells in vitro: effects of cell shape, cell-matrix interactions and cell-cell interactions Biochim Biophys Acta 1987 931 143 156 3663713
- [27]Sato T Vries RG Snippert HJ van de Wetering M Barker N Stange DE Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche Nature 2009 459 262 265 19329995
- [29]Sato T Stange DE Ferrante M Vries RG Van Es JH Van den Brink S Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium Gastroenterology 2011 141 1762 1772 21889923
- [30]Bartfeld S Bayram T van de Wetering M Huch M Begthel H Kujala P In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection Gastroenterology 2015 148 126 136.e6 25307862 PMC4274199
- [31]Yee C Dickson KA Muntasir MN Ma Y Marsh DJ Three-dimensional modelling of ovarian cancer: From cell lines to organoids for discovery and personalized medicine Front Bioeng Biotechnol 2022 10 836984 35223797 PMC8866972
- [33]Boj SF Hwang CI Baker LA Chio II Engle DD Corbo V Organoid models of human and mouse ductal pancreatic cancer Cell 2015 160 324 338 25557080 PMC4334572
- [34]Li X Francies HE Secrier M Perner J Miremadi A Galeano-Dalmau N Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics Nat Commun 2018 9 2983 30061675 PMC6065407
- [36]Martínez AK Maroni L Marzioni M Ahmed ST Milad M Ray D Mouse models of liver fibrosis mimic human liver fibrosis of different etiologies Curr Pathobiol Rep 2014 2 143 153 25396098 PMC4226463
- [37]Fiorotto R Amenduni M Mariotti V Fabris L Spirli C Strazzabosco M Liver diseases in the dish: iPSC and organoids as a new approach to modeling liver diseases Biochim Biophys Acta Mol Basis Dis 2019 1865 920 928 30264693 PMC6658095
- [39]Arzumanian VA Kiseleva OI Poverennaya EV The curious case of the HepG2 cell line: 40 years of expertise Int J Mol Sci 2021 22 13135 34884942 PMC8658661
- [41]Lam DTUH Dan YY Chan YS Ng HH Emerging liver organoid platforms and technologies Cell Regen 2021 10 27 34341842 PMC8329140
- [43]Fagiuoli S Daina E D’Antiga L Colledan M Remuzzi G Monogenic diseases that can be cured by liver transplantation J Hepatol 2013 59 595 612 23578885
- [44]Lachmann RH Enzyme replacement therapy for lysosomal storage diseases Curr Opin Pediatr 2011 23 588 593 21946346
- [45]Walshe JM Yealland M Chelation treatment of neurological Wilson’s disease Q J Med 1993 86 197 204 8369040
- [46]Boudes PF Gene therapy as a new treatment option for inherited monogenic diseases Eur J Intern Med 2014 25 31 36 24129166
- [48]Caiazza C Parisi S Caiazzo M Liver organoids: Updates on disease modeling and biomedical applications Biology (Basel) 2021 10 835 34571712 PMC8470787
- [49]Gómez-Mariano G Matamala N Martínez S Justo I Marcacuzco A Jimenez C Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease Hepatol Int 2020 14 127 137 31832977 PMC6994530
- [50]Fromme M Schneider CV Trautwein C Brunetti-Pierri N Strnad P Alpha-1 antitrypsin deficiency: A re-surfacing adult liver disorder J Hepatol 2022 76 946 958 34848258
- [51]Andersson ER Chivukula IV Hankeova S Sjöqvist M Tsoi YL Ramsköld D Mouse model of alagille syndrome and mechanisms of Jagged1 missense mutations Gastroenterology 2018 154 1080 1095 29162437 PMC7007299
- [52]Kruitwagen HS Oosterhoff LA van Wolferen ME Chen C Nantasanti Assawarachan S Schneeberger K Long-term survival of transplanted autologous canine liver organoids in a COMMD1-deficient dog model of metabolic liver disease Cells 2020 9 410 32053895 PMC7072637
- [53]Nantasanti S Spee B Kruitwagen HS Chen C Geijsen N Oosterhoff LA Disease modeling and gene therapy of copper storage disease in canine hepatic organoids Stem Cell Reports 2015 5 895 907 26455412 PMC4649105
- [55]Ogawa M Ogawa S Bear CE Ahmadi S Chin S Li B Directed differentiation of cholangiocytes from human pluripotent stem cells Nat Biotechnol 2015 33 853 861 26167630
- [56]Sampaziotis F de Brito MC Madrigal P Bertero A Saeb-Parsy K Soares FAC Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation Nat Biotechnol 2015 33 845 852 26167629 PMC4768345
- [57]Shinozawa T Kimura M Cai Y Saiki N Yoneyama Y Ouchi R High-fidelity drug-induced liver injury screen using human pluripotent stem cell-derived organoids Gastroenterology 2021 160 831 846.e10 33039464 PMC7878295
- [58]Ouchi R Togo S Kimura M Shinozawa T Koido M Koike H Modeling steatohepatitis in humans with pluripotent stem cell-derived organoids Cell Metab 2019 30 374 384.e6 31155493 PMC6687537
- [62]Akbari S Sevinç GG Ersoy N Basak O Kaplan K Sevinç K Robust, long-term culture of endoderm-derived hepatic organoids for disease modeling Stem Cell Reports 2019 13 627 641 31522975 PMC6829764
- [63]Graffmann N Scherer B Adjaye J In vitro differentiation of pluripotent stem cells into hepatocyte like cells - Basic principles and current progress Stem Cell Res 2022 61 102763 35395623
- [64]Kvist AJ Kanebratt KP Walentinsson A Palmgren H O’Hara M Björkbom A Critical differences in drug metabolic properties of human hepatic cellular models, including primary human hepatocytes, stem cell derived hepatocytes, and hepatoma cell lines Biochem Pharmacol 2018 155 124 140 29953844
- [65]Ma H de Zwaan E Guo YE Cejas P Thiru P van de Bunt M The nuclear receptor THRB facilitates differentiation of human PSCs into more mature hepatocytes. Cell Stem Cell 2022;29:795-809.e11 Erratum in: Cell Stem Cell 2022 29 1611 35452598 PMC9466295
- [66]Yang J Pan G Guan L Liu Z Wu Y Liu Z The burden of primary liver cancer caused by specific etiologies from 1990 to 2019 at the global, regional, and national levels Cancer Med 2022 11 1357 1370 34989144 PMC8894689
- [67]Saltsman JA Hammond WJ Narayan NJC Requena D Gehart H Lalazar G A human organoid model of aggressive hepatoblastoma for disease modeling and drug testing Cancers (Basel) 2020 12 2668 32962010 PMC7563272
- [68]Lin J Zhang H Yu H Bi X Zhang W Yin J Epidemiological characteristics of primary liver cancer in mainland China from 2003 to 2020: A representative multicenter study Front Oncol 2022 12 906778 35800051 PMC9253580
- [69]Piñero F Pages J Marciano S Fernández N Silva J Anders M Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina World J Hepatol 2018 10 41 50 29399277 PMC5787683
- [71]Al-Salama ZT Syed YY Scott LJ Lenvatinib: A review in hepatocellular carcinoma Drugs 2019 79 665 674 30993651
- [72]Personeni N Pressiani T Rimassa L Lenvatinib for the treatment of unresectable hepatocellular carcinoma: evidence to date J Hepatocell Carcinoma 2019 6 31 39 30775342 PMC6362912
- [73]Madden K Kasler MK Immune checkpoint inhibitors in lung cancer and melanoma Semin Oncol Nurs 2019 35 150932 31561846
- [74]Feng GS Hanley KL Liang Y Lin X Improving the efficacy of liver cancer immunotherapy: The power of combined preclinical and clinical studies Hepatology 2021 73 Suppl 1 104 114 PMC7854886 32715491
- [75]Marquardt JU Andersen JB Thorgeirsson SS Functional and genetic deconstruction of the cellular origin in liver cancer Nat Rev Cancer 2015 15 653 667 26493646
- [76]Ding X He M Chan AWH Song QX Sze SC Genomic and epigenomic features of primary and recurrent hepatocellular carcinomas Gastroenterology 2019 157 1630 1645.e6 31560893
- [78]Lin DC Mayakonda A Dinh HQ Huang P Lin L Liu X Genomic and epigenomic heterogeneity of hepatocellular carcinoma Cancer Res 2017 77 2255 2265 28302680 PMC5413372
- [79]Okrah K Tarighat S Liu B Koeppen H Wagle MC Cheng G Transcriptomic analysis of hepatocellular carcinoma reveals molecular features of disease progression and tumor immune biology NPJ Precis Oncol 2018 2 25 30456308 PMC6237857
- [80]Rebouissou S Franconi A Calderaro J Letouzé E Imbeaud S Pilati C Genotype-phenotype correlation of CTNNB1 mutations reveals different ß-catenin activity associated with liver tumor progression Hepatology 2016 64 2047 2061 27177928
- [81]Ishii T Tamura A Shibata T Kuroda K Kanda T Sugiyama M Analysis of HBV genomes integrated into the genomes of human hepatoma PLC/PRF/5 cells by HBV sequence capture-based next-generation sequencing Genes (Basel) 2020 11 661 32570699 PMC7348787
- [82]Kamatani Y Wattanapokayakit S Ochi H Kawaguchi T Takahashi A Hosono N A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians Nat Genet 2009 41 591 595 19349983
- [83]Sze KM Ho DW Chiu YT Tsui YM Chan LK Lee JM Hepatitis B Virus-telomerase reverse transcriptase promoter integration harnesses host ELF4, resulting in telomerase reverse transcriptase gene transcription in hepatocellular carcinoma Hepatology 2021 73 23 40 32170761 PMC7898544
- [84]Byrne CD Targher G NAFLD: a multisystem disease J Hepatol 2015 62 1 Suppl S47 S64 25920090
- [85]Curtius K Wright NA Graham TA An evolutionary perspective on field cancerization Nat Rev Cancer 2018 18 19 32 29217838
- [87]Takai A Fako V Dang H Forgues M Yu Z Budhu A Three-dimensional organotypic culture models of human hepatocellular carcinoma Sci Rep 2016 6 21174 26880118 PMC4754778
- [88]He X Hikiba Y Suzuki Y Nakamori Y Kanemaru Y Sugimori M EGFR inhibition reverses resistance to lenvatinib in hepatocellular carcinoma cells Sci Rep 2022 12 8007 35568782 PMC9107466
- [90]Xu H Lyu X Yi M Zhao W Song Y Wu K Organoid technology and applications in cancer research J Hematol Oncol 2018 11 116 30219074 PMC6139148
- [91]Wu LJ Chen ZY Wang Y Zhao JG Xie XZ Chen G Organoids of liver diseases: From bench to bedside World J Gastroenterol 2019 25 1913 1927 31086460 PMC6487380
- [92]El-Serag HB Rudolph KL Hepatocellular carcinoma: epidemiology and molecular carcinogenesis Gastroenterology 2007 132 2557 2576 17570226
- [93]Zhou C Zhang W Chen W Yin Y Atyah M Liu S Integrated analysis of copy number variations and gene expression profiling in hepatocellular carcinoma Sci Rep 2017 7 10570 28874807 PMC5585301
- [94]Li L Knutsdottir H Hui K Weiss MJ He J Philosophe B Human primary liver cancer organoids reveal intratumor and interpatient drug response heterogeneity JCI Insight 2019 4 e121490 30674722 PMC6413833
- [95]Cao W Li M Liu J Zhang S Noordam L Verstegen MMA LGR5 marks targetable tumor-initiating cells in mouse liver cancer Nat Commun 2020 11 1961 32327656 PMC7181628
- [97]Chan-On W Nairismägi ML Ong CK Lim WK Dima S Pairojkul C Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers Nat Genet 2013 45 1474 1478 24185513
- [98]Yang L Chen J Liang J Zhang Y Wang Q Ren X Modeling hepatoblastoma development with human fetal liver organoids reveals YAP1 activation is sufficient for tumorigenesis Protein Cell 2022 13 683 688 34893955 PMC9233724
- [99]Huch M Dorrell C Boj SF van Es JH Li VS van de Wetering M In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration Nature 2013 494 247 250 23354049 PMC3634804
- [100]Sun L Wang Y Cen J Ma X Cui L Qiu Z Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes Nat Cell Biol 2019 21 1015 1026 31332348
- [101]Huang P Zhang L Gao Y He Z Yao D Wu Z Direct reprogramming of human fibroblasts to functional and expandable hepatocytes Cell Stem Cell 2014 14 370 384 24582927
- [102]Zheng K Cubero FJ Nevzorova YA c-MYC-making liver sick: Role of c-MYC in hepatic cell function, homeostasis and disease Genes (Basel) 2017 8 123 28422055 PMC5406870
- [103]Sun L Hui L Progress in human liver organoids J Mol Cell Biol 2020 12 607 617 32236564 PMC7683012
- [104]Dijkstra KK Monkhorst K Schipper LJ Hartemink KJ Smit EF Kaing S Challenges in establishing pure lung cancer organoids limit their utility for personalized medicine Cell Rep 2020 31 107588 32375033
- [106]Fujii M Shimokawa M Date S Takano A Matano M Nanki K A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis Cell Stem Cell 2016 18 827 838 27212702
- [107]Cao W Liu J Wang L Li M Verstegen MMA Yin Y Modeling liver cancer and therapy responsiveness using organoids derived from primary mouse liver tumors Carcinogenesis 2019 40 145 154 30289434
- [108]Protzer U Maini MK Knolle PA Living in the liver: hepatic infections Nat Rev Immunol 2012 12 201 213 22362353
- [110]Fanning GC Zoulim F Hou J Bertoletti A Therapeutic strategies for hepatitis B virus infection: towards a cure. Nat Rev Drug Discov 2019;18:827-844 Erratum in: Nat Rev Drug Discov 2020 19 291 31913354
- [111]Roca Suarez AA Testoni B Zoulim F HBV 2021: New therapeutic strategies against an old foe Liver Int 2021 41 Suppl 1 15 23 34155787
- [112]Degasperi E Anolli MP Lampertico P Bulevirtide for patients with compensated chronic hepatitis delta: A review Liver Int 2022 Aug 9 doi: 10.1111/liv.15389 35942695 · DOI
- [113]Nassal M HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B Gut 2015 64 1972 1984 26048673
- [114]Manns MP Maasoumy B Breakthroughs in hepatitis C research: from discovery to cure Nat Rev Gastroenterol Hepatol 2022 19 533 550 35595834 PMC9122245
- [115]Kolykhalov AA Agapov EV Blight KJ Mihalik K Feinstone SM Rice CM Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA Science 1997 277 570 574 9228008
- [116]Yanagi M Purcell RH Emerson SU Bukh J Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee Proc Natl Acad Sci U S A 1997 94 8738 8743 9238047 PMC23104
- [117]Baktash Y Madhav A Coller KE Randall G Single particle imaging of polarized hepatoma organoids upon hepatitis C virus infection reveals an ordered and sequential entry process Cell Host Microbe 2018 23 382 394.e5 29544098 PMC7169308
- [118]Ko C Lee S Windisch MP Ryu WS DDX3 DEAD-box RNA helicase is a host factor that restricts hepatitis B virus replication at the transcriptional level J Virol 2014 88 13689 13698 25231298 PMC4248967
- [119]Nishitsuji H Harada K Ujino S Zhang J Kohara M Sugiyama M Investigating the hepatitis B virus life cycle using engineered reporter hepatitis B viruses Cancer Sci 2018 109 241 249 29121422 PMC5765299
- [120]Verrier ER Colpitts CC Bach C Heydmann L Weiss A Renaud M A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses Hepatology 2016 63 35 48 26224662
- [121]Lucifora J Durantel D Testoni B Hantz O Levrero M Zoulim F Control of hepatitis B virus replication by innate response of HepaRG cells Hepatology 2010 51 63 72 19877170
- [122]Macovei A Radulescu C Lazar C Petrescu S Durantel D Dwek RA Hepatitis B virus requires intact caveolin-1 function for productive infection in HepaRG cells J Virol 2010 84 243 253 19846513 PMC2798426
- [123]Ni Y Lempp FA Mehrle S Nkongolo S Kaufman C Fälth M Hepatitis B and D viruses exploit sodium taurocholate cotransporting polypeptide for species-specific entry into hepatocytes Gastroenterology 2014 146 1070 1083 24361467
- [124]Schulze A Gripon P Urban S Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans Hepatology 2007 46 1759 1768 18046710
- [125]Sureau C Salisse J A conformational heparan sulfate binding site essential to infectivity overlaps with the conserved hepatitis B virus a-determinant Hepatology 2013 57 985 994 23161433
- [126]Hantz O Parent R Durantel D Gripon P Guguen-Guillouzo C Zoulim F Persistence of the hepatitis B virus covalently closed circular DNA in HepaRG human hepatocyte-like cells J Gen Virol 2009 90 127 135 19088281
- [127]Sakurai F Mitani S Yamamoto T Takayama K Tachibana M Watashi K Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection Sci Rep 2017 7 45698 28374759 PMC5379564
- [128]Shlomai A Schwartz RE Ramanan V Bhatta A de Jong YP Bhatia SN Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems Proc Natl Acad Sci U S A 2014 111 12193 12198 25092305 PMC4143014
- [129]Xia Y Carpentier A Cheng X Block PD Zhao Y Zhang Z Human stem cell-derived hepatocytes as a model for hepatitis B virus infection, spreading and virus-host interactions J Hepatol 2017 66 494 503 27746336 PMC5316493
- [130]Nie YZ Zheng YW Miyakawa K Murata S Zhang RR Sekine K Recapitulation of hepatitis B virus-host interactions in liver organoids from human induced pluripotent stem cells EBioMedicine 2018 35 114 123 30120080 PMC6156717
- [131]De Crignis E Hossain T Romal S Carofiglio F Moulos P Khalid MM Application of human liver organoids as a patient-derived primary model for HBV infection and related hepatocellular carcinoma Elife 2021 10 e60747 34328417 PMC8384419
- [132]Medhat A Arzumanyan A Feitelson MA Hepatitis B x antigen (HBx) is an important therapeutic target in the pathogenesis of hepatocellular carcinoma Oncotarget 2021 12 2421 2433 34853663 PMC8629409
- [133]Ma XX Ji Y Jin L Baloch Z Zhang DR Wang Y Prevalence and clinical features of hepatitis E virus infection in pregnant women: A large cohort study in Inner Mongolia, China Clin Res Hepatol Gastroenterol 2021 45 101536 33051171
- [134]Kinast V Burkard TL Todt D Steinmann E Hepatitis E virus drug development Viruses 2019 11 485 31141919 PMC6631701
- [135]Li P Li Y Wang Y Liu J Lavrijsen M Li Y Recapitulating hepatitis E virus-host interactions and facilitating antiviral drug discovery in human liver-derived organoids Sci Adv 2022 8 eabj5908 35044825 PMC8769558
- [136]Yang L Han Y Nilsson-Payant BE Gupta V Wang P Duan X A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids Cell Stem Cell 2020 27 125 136.e7 32579880 PMC7303620
- [137]Richards A Friesen M Khalil A Barrasa MI Gehrke L Jaenisch R SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology iScience 2022 25 105146 36128218 PMC9477603
- [138]Zhao B Ni C Gao R Wang Y Yang L Wei J Recapitulation of SARS-CoV-2 infection and cholangiocyte damage with human liver ductal organoids Protein Cell 2020 11 771 775 32303993 PMC7164704
- [139]Zhao Y Ren X Lu J He M Liu Z Yi L Mechanistic insight of SARS-CoV-2 infection using human hepatobiliary organoids Gut 2023 72 216 218 35459707 PMC9763169
- [140]McCarron S Bathon B Conlon DM Abbey D Rader DJ Gawronski K Functional characterization of organoids derived from irreversibly damaged liver of patients with NASH Hepatology 2021 74 1825 1844 33901295 PMC12928191
- [141]Lagana SM Kudose S Iuga AC Lee MJ Fazlollahi L Remotti HE Hepatic pathology in patients dying of COVID-19: a series of 40 cases including clinical, histologic, and virologic data Mod Pathol 2020 33 2147 2155 32792598 PMC7424245
- [142]Wang Y Liu S Liu H Li W Lin F Jiang L SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19 J Hepatol 2020 73 807 816 32437830 PMC7211738
- [143]Weber S Hellmuth JC Scherer C Muenchhoff M Mayerle J Gerbes AL Liver function test abnormalities at hospital admission are associated with severe course of SARS-CoV-2 infection: a prospective cohort study Gut 2021 70 1925 1932 33514597 PMC7852072
- [144]Muus C Luecken MD Eraslan G Sikkema L Waghray A Heimberg G NHLBI LungMap Consortium Human Cell Atlas Lung Biological Network Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics Nat Med 2021 27 546 559 33654293 PMC9469728
- [145]Ji D Qin E Xu J Zhang D Cheng G Wang Y Non-alcoholic fatty liver diseases in patients with COVID-19: A retrospective study J Hepatol 2020 73 451 453 32278005 PMC7141624
- [146]Loomba R Sanyal AJ The global NAFLD epidemic Nat Rev Gastroenterol Hepatol 2013 10 686 690 24042449
- [147]Younossi ZM Koenig AB Abdelatif D Fazel Y Henry L Wymer M Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes Hepatology 2016 64 73 84 26707365
- [148]Boeckmans J Natale A Buyl K Rogiers V De Kock J Vanhaecke T Human-based systems: Mechanistic NASH modelling just around the corner? Pharmacol Res 2018 134 257 267 29964161
- [149]Li Z Xue J Chen P Chen L Yan S Liu L Prevalence of nonalcoholic fatty liver disease in mainland of China: a meta-analysis of published studies J Gastroenterol Hepatol 2014 29 42 51 24219010
- [150]Estes C Anstee QM Arias-Loste MT Bantel H Bellentani S Caballeria J Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030 J Hepatol 2018 69 896 904 29886156
- [151]Wong RJ Aguilar M Cheung R Perumpail RB Harrison SA Younossi ZM Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States Gastroenterology 2015 148 547 555 25461851
- [152]Berná G Romero-Gomez M The role of nutrition in non-alcoholic fatty liver disease: Pathophysiology and management Liver Int 2020 40 Suppl 1 102 108 32077594
- [153]Bazick J Donithan M Neuschwander-Tetri BA Kleiner D Brunt EM Wilson L Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD: Guidelines for referral in NAFLD Diabetes Care 2015 38 1347 1355 25887357 PMC4477334
- [154]Huang PL A comprehensive definition for metabolic syndrome Dis Model Mech 2009 2 231 237 19407331 PMC2675814
- [155]Portillo-Sanchez P Bril F Maximos M Lomonaco R Biernacki D Orsak B High prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and normal plasma aminotransferase levels J Clin Endocrinol Metab 2015 100 2231 2238 25885947 PMC6287506
- [156]Schwimmer JB Celedon MA Lavine JE Salem R Campbell N Schork NJ Heritability of nonalcoholic fatty liver disease Gastroenterology 2009 136 1585 1592 19208353 PMC3397140
- [157]Anstee QM Darlay R Cockell S Meroni M Govaere O Tiniakos D EPoS Consortium Investigators Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort. J Hepatol 2020;73:505-515 Erratum in: J Hepatol 2021 74 1274 1275 Erratum in: J Hepatol 2023 Mar 13. doi: 10.1016/j.jhep.2023.02.028 33678471 · DOI
- [159]Gerges SH Wahdan SA Elsherbiny DA El-Demerdash E Non-alcoholic fatty liver disease: An overview of risk factors, pathophysiological mechanisms, diagnostic procedures, and therapeutic interventions Life Sci 2021 271 119220 33592199
- [160]Satapathy SK Sanyal AJ Epidemiology and natural history of nonalcoholic fatty liver disease Semin Liver Dis 2015 35 221 235 26378640
- [161]Wang XJ Malhi H Nonalcoholic fatty liver disease Ann Intern Med 2018 169 ITC65 ITC80 30398639
- [162]Day CP James OF Steatohepatitis: a tale of two “hits”? Gastroenterology 1998 114 842 845 9547102
- [163]Buzzetti E Pinzani M Tsochatzis EA The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD) Metabolism 2016 65 1038 1048 26823198
- [164]Fukuda N Ontko JA Interactions between fatty acid synthesis, oxidation, and esterification in the production of triglyceride-rich lipoproteins by the liver J Lipid Res 1984 25 831 842 6491528
- [165]Caligiuri A Gentilini A Marra F Molecular pathogenesis of NASH Int J Mol Sci 2016 17 1575 27657051 PMC5037841
- [166]Takaki A Kawai D Yamamoto K Molecular mechanisms and new treatment strategies for non-alcoholic steatohepatitis (NASH) Int J Mol Sci 2014 15 7352 7379 24786095 PMC4057677
- [167]Alisi A Carpino G Oliveira FL Panera N Nobili V Gaudio E The role of tissue macrophage-mediated inflammation on NAFLD pathogenesis and its clinical implications Mediators Inflamm 2017 2017 8162421 28115795 PMC5237469
- [168]Deng CJ Lo TH Chan KY Li X Wu MY Xiang Z Role of B lymphocytes in the pathogenesis of NAFLD: A 2022 update Int J Mol Sci 2022 23 12376 36293233 PMC9603875
- [169]Gehrke N Schattenberg JM Metabolic inflammation-A role for hepatic inflammatory pathways as drivers of comorbidities in nonalcoholic fatty liver disease? Gastroenterology 2020 158 1929 1947.e6 32068022
- [170]Hassan K Bhalla V El Regal ME A-Kader HH Nonalcoholic fatty liver disease: a comprehensive review of a growing epidemic World J Gastroenterol 2014 20 12082 12101 25232245 PMC4161796
- [172]Peverill W Powell LW Skoien R Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation Int J Mol Sci 2014 15 8591 8638 24830559 PMC4057750
- [173]Hansen HH Feigh M Veidal SS Rigbolt KT Vrang N Mouse models of nonalcoholic steatohepatitis in preclinical drug development Drug Discov Today 2017 22 1707 1718 28687459
- [175]Chen W Chang B Li L Chan L Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology 2010;52:1134-1142 Erratum in: Hepatology 2010 52 2250 PMC2932863 20648554
- [176]Tilson SG Morell CM Lenaerts AS Park SB Hu Z Jenkins B Modeling PNPLA3-associated NAFLD using human-induced pluripotent stem cells Hepatology 2021 74 2998 3017 34288010 PMC11497257
- [177]Kershaw EE Hamm JK Verhagen LA Peroni O Katic M Flier JS Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin Diabetes 2006 55 148 157 16380488 PMC2819178
- [178]Lake AC Sun Y Li JL Kim JE Johnson JW Li D Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members J Lipid Res 2005 46 2477 2487 16150821
- [180]Collin de l’Hortet A Takeishi K Guzman-Lepe J Morita K Achreja A Popovic B Generation of human fatty livers using custom-engineered induced pluripotent stem cells with modifiable SIRT1 metabolism Cell Metab 2019 30 385 401.e9 31390551 PMC6691905
- [181]Kimura M Iguchi T Iwasawa K Dunn A Thompson WL Yoneyama Y En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH Cell 2022 185 4216 4232.e16 36240780 PMC9617783
- [182]Wang S Wang X Tan Z Su Y Liu J Chang M Human ESCderived expandable hepatic organoids enable therapeutic liver repopulation and pathophysiological modeling of alcoholic liver injury Cell Res 2019 29 1009 1026 31628434 PMC6951343
- [183]Singh S Allen AM Wang Z Prokop LJ Murad MH Loomba R Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies Clin Gastroenterol Hepatol 2015 13 643 654.e1-9 quiz e39-40 24768810 PMC4208976
- [185]Chen Y Gao WK Shu YY Ye J Mechanisms of ductular reaction in non-alcoholic steatohepatitis World J Gastroenterol 2022 28 2088 2099 35664038 PMC9134136
- [186]Ben-Moshe S Itzkovitz S Spatial heterogeneity in the mammalian liver Nat Rev Gastroenterol Hepatol 2019 16 395 410 30936469
- [187]Purushotham A Schug TT Xu Q Surapureddi S Guo X Li X Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation Cell Metab 2009 9 327 338 19356714 PMC2668535
- [188]Bhatia SN Ingber DE Microfluidic organs-on-chips Nat Biotechnol 2014 32 760 772 25093883
- [190]Ratziu V Friedman SL Why do so many NASH trials fail? Gastroenterology 2020 May 18 doi: 10.1053/j.gastro.2020.05.046 · DOI · Paper page
- [191]Neuschwander-Tetri BA Loomba R Sanyal AJ Lavine JE Van Natta ML Abdelmalek MF NASH Clinical Research Network Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 2015;385:956-965. Erratum in: Lancet 2015;385:946 Erratum in: Lancet 2016 387 1618 PMC4447192 25468160
- [193]Takebe T Taniguchi H Human iPSC-derived miniature organs: a tool for drug studies Clin Pharmacol Ther 2014 96 310 313 24848506
- [194]Yang K Woodhead JL Watkins PB Howell BA Brouwer KL Systems pharmacology modeling predicts delayed presentation and species differences in bile acid-mediated troglitazone hepatotoxicity Clin Pharmacol Ther 2014 96 589 598 25068506 PMC4480860
- [196]Russmann S Kullak-Ublick GA Grattagliano I Current concepts of mechanisms in drug-induced hepatotoxicity Curr Med Chem 2009 16 3041 3053 19689281 PMC2765083
- Authors
- Liu, Y., Sheng, J.-Y., Yang, C.-F., Ding, J., & Chan, Y.-S.
- Affiliations
- Sun Yat-sen University (CN)
- Guangzhou Laboratory (CN)
- Corresponding author
- Chan, Yun-Shen
- Venue
- Clinical and Molecular Hepatology
- Published
- 2023-07-01
- Volume
- 29
- Issue
- 3
- Pages
- 643-669
- ISSN
- 2287-2728 (ISSN-L)
- 2287-285X
- PMC
- PMC10366802
- OpenAlex
- W4323348441
- Cited by
- 30
- References
- 196
- Citations by year
- 2026: 15 · 2025: 6 · 2024: 8 · 2023: 1
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Clinical and Molecular Hepatology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- liver organoids, disease modeling, pluripotent stem cell differentiation, patient-derived organoids, hereditary liver disease, primary liver cancer, viral hepatitis, non-alcoholic fatty liver disease, regenerative therapy, personalized medicine
- MeSH terms
- Cell Differentiation, Humans, Liver Diseases, Organoids
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