Abstract
Reliable in vitro models with human-derived cells that recapitulate in vivo-like physiologies are required for drug discovery and development to reduce the gap between the results of cell-based drug testing, animal testing, and human clinical trials. Liver organoid models have emerged as novel tools for hepatotoxicity evaluation, liver disease modeling, and drug screening. Liver organoids can be generated from biopsies of liver tissues or pluripotent stem cells and can be applied to various liver diseases, including metabolic associated fatty liver disease, infectious liver disease, genetic liver disease, and liver cancer. This review focuses on recent studies on organoids to model human liver diseases and discusses the advantages and limitations of current liver organoids for translational applications.
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References
Aberle MR, Burkhart RA, Tiriac H, Olde Damink S, Dejong CH, Tuveson DA, van Dam RM (2018) Patient-derived organoid models help define personalized management of gastrointestinal cancer. J Br Surg 105:e48–e60. https://doi.org/10.1002/bjs.10726
Achberger K, Probst C, Haderspeck J, Bolz S, Rogal J, Chuchuy J, Nikolova M, Cora V, Antkowiak L, Haq W (2019) Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform. Elife 8:e46188. https://doi.org/10.7554/eLife.46188.001
Akbari S, Sevinc GG, Ersoy N, Basak O, Kaplan K, Sevinc K, Ozel E, Sengun B, Enustun E, Ozcimen B, Bagriyanik A, Arslan N, Onder TT, Erdal E (2019) Robust, long-term culture of endoderm-derived hepatic organoids for disease modeling. Stem Cell Rep 13:627–641. https://doi.org/10.1016/j.stemcr.2019.08.007
Aleksandrova K, Stelmach-Mardas M, Schlesinger S (2016) Obesity and liver cancer. Recent Results Cancer Research 208:177–198. https://doi.org/10.1007/978-3-319-42542-9_10
Artegiani B, van Voorthuijsen L, Lindeboom RGH, Seinstra D, Heo I, Tapia P, Lopez-Iglesias C, Postrach D, Dayton T, Oka R, Hu H, van Boxtel R, van Es JH, Offerhaus J, Peters PJ, van Rheenen J, Vermeulen M, Clevers H (2019) Probing the tumor suppressor function of BAP1 in CRISPR-engineered human liver organoids. Cell Stem Cell 24(927–943):e926. https://doi.org/10.1016/j.stem.2019.04.017
Asai A, Aihara E, Watson C, Mourya R, Mizuochi T, Shivakumar P, Phelan K, Mayhew C, Helmrath M, Takebe T, Wells J, Bezerra JA (2017) Paracrine signals regulate human liver organoid maturation from induced pluripotent stem cells. Development 144:1056–1064. https://doi.org/10.1242/dev.142794
Asrani SK, Devarbhavi H, Eaton J, Kamath PS (2019) Burden of liver diseases in the world. J Hepatol 70:151–171. https://doi.org/10.1016/j.jhep.2018.09.014
Avior Y, Levy G, Zimerman M, Kitsberg D, Schwartz R, Sadeh R, Moussaieff A, Cohen M, Itskovitz-Eldor J, Nahmias Y (2015) Microbial-derived lithocholic acid and vitamin K2 drive the metabolic maturation of pluripotent stem cells-derived and fetal hepatocytes. Hepatology 62:265–278. https://doi.org/10.1002/hep.27803
Baktash Y, Madhav A, Coller KE, Randall G (2018) Single particle imaging of polarized hepatoma organoids upon hepatitis C virus infection reveals an ordered and sequential entry process. Cell Host Microbe 23(382–394):e385. https://doi.org/10.1016/j.chom.2018.02.005
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
Brooks A, Liang X, Zhang Y, Zhao C-X, Roberts MS, Wang H, Zhang L, Crawford DH (2021) Liver organoid as a 3D in vitro model for drug validation and toxicity assessment. Pharmacol Res. https://doi.org/10.1016/j.phrs.2021.105608
Broutier L, Mastrogiovanni G, Verstegen MM, Francies HE, Gavarro LM, Bradshaw CR, Allen GE, Arnes-Benito R, Sidorova O, Gaspersz MP, Georgakopoulos N, Koo BK, Dietmann S, Davies SE, Praseedom RK, Lieshout R (2017) Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med 23:1424–1435. https://doi.org/10.1038/nm.4438
Bruix J, Han K-H, Gores G, Llovet JM, Mazzaferro V (2015) Liver cancer: approaching a personalized care. J Hepatol 62:S144–S156. https://doi.org/10.1016/j.jhep.2015.02.007
Chen C, Soto-Gutierrez A, Baptista PM, Spee B (2018) Biotechnology challenges to in vitro maturation of hepatic stem cells. Gastroenterology 154:1258–1272. https://doi.org/10.1053/j.gastro.2018.01.066
Chen YF, Tseng CY, Wang HW, Kuo HC, Yang VW, Lee OK (2012) Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol. Hepatology 55:1193–1203. https://doi.org/10.1002/hep.24790
Cheng Y-S, Li R, Baskfield A, Beers J, Zou J, Liu C, Zheng W (2019) A human induced pluripotent stem cell line (TRNDi007-B) from an infantile onset Pompe patient carrying p. R854X mutation in the GAA gene. Stem Cell Research 37:101435. https://doi.org/10.1016/j.scr.2019.101435
Corbett JL, Duncan SA (2019) iPSC-derived hepatocytes as a platform for disease modeling and drug discovery. Front Med 6:265. https://doi.org/10.3389/fmed.2019.00265
De Crignis E, Hossain T, Romal S, Carofiglio F, Moulos P, Khalid MM, Rao S, Bazrafshan A, Verstegen MM, Pourfarzad F (2021) Application of human liver organoids as a patient-derived primary model for HBV infection and related hepatocellular carcinoma. Elife 10:e60747. https://doi.org/10.7554/eLife.60747
Everitt JI (2015) The future of preclinical animal models in pharmaceutical discovery and development: a need to bring in cerebro to the in vivo discussions. Toxicol Pathol 43:70–77. https://doi.org/10.1177/0192623314555162
Fouad Y, Waked I, Bollipo S, Gomaa A, Ajlouni Y, Attia D (2020) What’s in a name? Renaming “NAFLD” to “MAFLD.” Liver Int 40:1254–1261. https://doi.org/10.1111/liv.14478
Gamboa CM, Wang Y, Xu H, Kalemba K, Wondisford FE, Sabaawy HE (2021) Optimized 3D culture of hepatic cells for liver organoid metabolic assays. Cells. https://doi.org/10.3390/cells10123280
Ghodsizadeh A, Taei A, Totonchi M, Seifinejad A, Gourabi H, Pournasr B, Aghdami N, Malekzadeh R, Almadani N, Salekdeh GH (2010) Generation of liver disease-specific induced pluripotent stem cells along with efficient differentiation to functional hepatocyte-like cells. Stem Cell Reviews and Reports 6:622–632. https://doi.org/10.1007/s12015-010-9189-3
Gomez-Mariano G, Matamala N, Martinez S, Justo I, Marcacuzco A, Jimenez C, Monzon S, Cuesta I, Garfia C, Martinez MT, Huch M, Perez de Castro I, Posada M, Janciauskiene S, Martinez-Delgado B (2020) Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease. Hep Intl 14:127–137. https://doi.org/10.1007/s12072-019-10007-y
Guan Y, Enejder A, Wang M, Fang Z, Cui L, Chen SY, Wang J, Tan Y, Wu M, Chen X, Johansson PK, Osman I, Kunimoto K, Russo P, Heilshorn SC, Peltz G (2021) A human multi-lineage hepatic organoid model for liver fibrosis. Nature Communication 12:6138. https://doi.org/10.1038/s41467-021-26410-9
Guan Y, Xu D, Garfin PM, Ehmer U, Hurwitz M, Enns G, Michie S, Wu M, Zheng M, Nishimura T (2017) Human hepatic organoids for the analysis of human genetic diseases. JCI Insight. https://doi.org/10.1172/jci.insight.94954
Gurevich I, Burton SA, Munn C, Ohshima M, Goedland ME, Czysz K, Rajesh D (2020) iPSC-derived hepatocytes generated from NASH donors provide a valuable platform for disease modeling and drug discovery. Biology Open. https://doi.org/10.1242/bio.055087
Hannan NR, Segeritz CP, Touboul T, Vallier L (2013) Production of hepatocyte-like cells from human pluripotent stem cells. Nature Protocol 8:430–437. https://doi.org/10.1038/nprot.2012.153
Harrer S, Shah P, Antony B, Hu J (2019) Artificial intelligence for clinical trial design. Trends in Pharmacological Science 40:577–591. https://doi.org/10.1016/j.tips.2019.05.005
Herland A, Maoz BM, Das D, Somayaji MR, Prantil-Baun R, Novak R, Cronce M, Huffstater T, Jeanty SS, Ingram M (2020) Quantitative prediction of human drug pharmacokinetic responses using multiple vascularized organ chips coupled by fluid transfer. Nature Biomedical Engineering 4:421. https://doi.org/10.1038/s41551-019-0498-9
Hong K-J, Seo S-H (2018) Organoid as a culture system for viral vaccine strains. Clinical and Experimental Vaccine Research 7:145–148. https://doi.org/10.7774/cevr.2018.7.2.145
Hu H, Gehart H, Artegiani B (2018) Long-term expansion of functional mouse and human hepatocytes as 3D organoids. Cell 175(1591–1606):e1519. https://doi.org/10.1016/j.cell.2018.11.013
Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen MM, Ellis E, van Wenum M, Fuchs SA, de Ligt J, van de Wetering M, Sasaki N, Boers SJ, Kemperman H, de Jonge J, Ijzermans JN, Nieuwenhuis EE, Hoekstra R, Strom S, Vries RR, van der Laan LJ, Cuppen E, Clevers H (2015) Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160:299–312. https://doi.org/10.1016/j.cell.2014.11.050
Im I, Jang MJ, Park SJ, Lee SH, Choi JH, Yoo HW, Kim S, Han YM (2015) Mitochondrial respiratory defect causes dysfunctional lactate turnover via AMP-activated protein kinase activation in human-induced pluripotent stem cell-derived hepatocytes. J Biol Chem 290:29493–29505. https://doi.org/10.1074/jbc.M115.670364
Kimura H, Sakai Y, Fujii T (2018) Organ/body-on-a-chip based on microfluidic technology for drug discovery. Drug Metab Pharmacokinet 33:43–48. https://doi.org/10.1016/j.dmpk.2017.11.003
Koike H, Iwasawa K, Ouchi R, Maezawa M, Giesbrecht K, Saiki N, Ferguson A, Kimura M, Thompson WL, Wells JM, Zorn AM, Takebe T (2019) Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary. Nature 574:112–116. https://doi.org/10.1038/s41586-019-1598-0
Koui Y, Kido T, Ito T, Oyama H, Chen SW, Katou Y, Shirahige K, Miyajima A (2017) An in vitro human liver model by iPSC-derived parenchymal and non-parenchymal cells. Stem Cell Rep 9:490–498. https://doi.org/10.1016/j.stemcr.2017.06.010
Lehmann V, Schene IF, Ardisasmita AI, Liv N, Veenendaal T, Klumperman J, van der Doef HP, Verkade HJ, Verstegen MM, van der Laan LJ (2021) The potential and limitations of intrahepatic cholangiocyte organoids to study inborn errors of metabolism. J Inherit Metab Dis. https://doi.org/10.1002/jimd.12450
Li L, Knutsdottir H, Hui K, Weiss MJ, He J, Philosophe B, Cameron AM, Wolfgang CL, Pawlik TM, Ghiaur G, Ewald AJ, Mezey E, Bader JS, Selaru FM (2019) Human primary liver cancer organoids reveal intratumor and interpatient drug response heterogeneity. JCI Insight. https://doi.org/10.1172/jci.insight.121490
Liu J, Li P, Wang L, Li M, Ge Z, Noordam L, Lieshout R, Verstegen MM, Ma B, Su J (2021) Cancer-associated fibroblasts provide a stromal niche for liver cancer organoids that confers trophic effects and therapy resistance. Cell Mol Gastroenterol Hepatol 11:407–431. https://doi.org/10.1016/j.jcmgh.2020.09.003
Malnick S, Maor Y (2020) The interplay between alcoholic liver disease, obesity, and the metabolic syndrome. Visc Med 36:198–205. https://doi.org/10.1159/000507233
Marsee A, Roos FJM, Verstegen MMA, Consortium HPBO, Gehart H, de Koning E, Lemaigre F, Forbes SJ, Peng WC, Huch M, Takebe T, Vallier L, Clevers H, van der Laan LJW and Spee B (2021) Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids. Cell Stem Cell 28:816–832. https://doi.org/10.1016/j.stem.2021.04.005
McCarron S, Bathon B, Conlon DM, Abbey D, Rader DJ, Gawronski K, Brown CD, Olthoff KM, Shaked A, Raabe TD (2021) Functional characterization of organoids derived from irreversibly damaged liver of patients with NASH. Hepatology 74:1825–1844. https://doi.org/10.1002/hep.31857
Miranda CC, Fernandes TG, Diogo MM, Cabral J (2018) Towards multi-organoid systems for drug screening applications. Bioengineering 5:49. https://doi.org/10.3390/bioengineering5030049
Mun SJ, Hong YH, Ahn HS, Ryu JS, Chung KS, Son MJ (2020) Long-term expansion of functional human pluripotent stem cell-derived hepatic organoids. Int J Stem Cells 13:279–286. https://doi.org/10.15283/ijsc20060
Mun SJ, Lee J, Chung KS, Son MY, Son MJ (2021) Effect of microbial short-chain fatty acids on CYP3A4-mediated metabolic activation of human pluripotent stem cell-derived liver organoids. Cells. https://doi.org/10.3390/cells10010126
Mun SJ, Ryu JS, Lee MO, Son YS, Oh SJ, Cho HS, Son MY, Kim DS, Kim SJ, Yoo HJ, Lee HJ, Kim J, Jung CR, Chung KS, Son MJ (2019) Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids. J Hepatol 71:970–985. https://doi.org/10.1016/j.jhep.2019.06.030
Ng SS, Saeb-Parsy K, Blackford SJ, Segal JM, Serra MP, Horcas-Lopez M, Mastoridis S, Jassem W, Frank CW, Cho NJ (2018) Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold. Biomaterials 182:299–311. https://doi.org/10.1016/j.biomaterials.2018.07.043
Nie YZ, Zheng YW, Miyakawa K, Murata S, Zhang RR, Sekine K, Ueno Y, Takebe T, Wakita T, Ryo A, Taniguchi H (2018) Recapitulation of hepatitis B virus-host interactions in liver organoids from human induced pluripotent stem cells. EBioMedicine 35:114–123. https://doi.org/10.1016/j.ebiom.2018.08.014
Nuciforo S, Fofana I, Matter MS, Blumer T, Calabrese D, Boldanova T, Piscuoglio S, Wieland S, Ringnalda F, Schwank G, Terracciano LM, Ng CKY, Heim MH (2018) Organoid models of human liver cancers derived from tumor needle biopsies. Cell Rep 24:1363–1376. https://doi.org/10.1016/j.celrep.2018.07.001
Nuciforo S, Heim MH (2021) Organoids to model liver disease. JHEP Rep 3:100198. https://doi.org/10.1016/j.jhepr.2020.100198
Olgasi C, Cucci A, Follenzi A (2020) iPSC-derived liver organoids: a journey from drug screening, to disease modeling, arriving to regenerative medicine. Int J Mol Sci. https://doi.org/10.3390/ijms21176215
Ouchi R, Togo S, Kimura M, Shinozawa T, Koido M, Koike H, Thompson W, Karns RA, Mayhew CN, McGrath PS, McCauley HA, Zhang RR, Lewis K, Hakozaki S, Ferguson A, Saiki N, Yoneyama Y, Takeuchi I, Mabuchi Y, Akazawa C, Yoshikawa HY, Wells JM, Takebe T (2019) Modeling steatohepatitis in humans with pluripotent stem cell-derived organoids. Cell Metab 30(374–384):e376. https://doi.org/10.1016/j.cmet.2019.05.007
Overeem AW, Klappe K, Parisi S, Kloters-Planchy P, Matakovic L, du Teil EM, Drouin CA, Weiss KH (2019) Pluripotent stem cell-derived bile canaliculi-forming hepatocytes to study genetic liver diseases involving hepatocyte polarity. J Hepatol 71:344–356. https://doi.org/10.1016/j.jhep.2019.03.031
Panwar A, Das P, Tan LP (2021) 3D hepatic organoid-based advancements in LIVER tissue engineering. Bioengineering. https://doi.org/10.3390/bioengineering8110185
Ramakrishna G, Babu PE, Singh R, Trehanpati N (2021) Application of CRISPR-Cas9 based gene editing to study the pathogenesis of colon and liver cancer using organoids. Hep Intl. https://doi.org/10.1007/s12072-021-10237-z
Ramli MNB, Lim YS, Koe CT, Demircioglu D, Tng W, Gonzales KAU, Tan CP, Szczerbinska I, Liang H, Soe EL (2020) Human pluripotent stem cell-derived organoids as models of liver disease. Gastroenterology 159(1471–1486):e1412. https://doi.org/10.1053/j.gastro.2020.06.010
Ramme AP, Koenig L, Hasenberg T, Schwenk C, Magauer C, Faust D, Lorenz AK, Krebs A-C, Drewell C, Schirrmann K (2019) Autologous induced pluripotent stem cell-derived four-organ-chip. Fut Sci 5:413. https://doi.org/10.2144/fsoa-2019-0065
Ramos MJ, Bandiera L, Menolascina F, Fallowfield JA (2022) In vitro models for non-alcoholic fatty liver disease: emerging platforms and their applications. iScience 25:103549. https://doi.org/10.1016/j.isci.2021.103549
Rao S, Hossain T, Mahmoudi T (2021) 3D human liver organoids: an in vitro platform to investigate HBV infection, replication and liver tumorigenesis. Cancer Lett 506:35–44. https://doi.org/10.1016/j.canlet.2021.02.024
Rashid ST, Corbineau S, Hannan N, Marciniak SJ, Miranda E, Alexander G, Huang-Doran I, Griffin J, Ahrlund-Richter L, Skepper J (2010) Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Investig 120:3127–3136. https://doi.org/10.1172/JCI43122
Rimland CA, Tilson SG, Morell CM, Tomaz RA, Lu WY, Adams SE, Georgakopoulos N, Otaizo-Carrasquero F, Myers TG, Ferdinand JR, Gieseck RL 3rd, Sampaziotis F, Tysoe OC, Ross A, Kraiczy JM, Wesley B, Muraro D, Zilbauer M, Oniscu GC, Hannan NRF, Forbes SJ, Saeb-Parsy K, Wynn TA, Vallier L (2021) Regional differences in human biliary tissues and corresponding in vitro-derived organoids. Hepatology 73:247–267. https://doi.org/10.1002/hep.31252
Roper J, Yilmaz OH (2019) Breakthrough moments: genome editing and organoids. Cell Stem Cell 24:841–842. https://doi.org/10.1016/j.stem.2019.05.008
Sampaziotis F, de Brito MC, Madrigal P, Bertero A, Saeb-Parsy K, Soares FAC, Schrumpf E, Melum E, Karlsen TH, Bradley JA, Gelson WT, Davies S, Baker A, Kaser A, Alexander GJ, Hannan NRF, Vallier L (2015) Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nat Biotechnol 33:845–852. https://doi.org/10.1038/nbt.3275
Satoh D, Maeda T, Ito T, Nakajima Y, Ohte M, Ukai A, Nakamura K, Enosawa S, Toyota M, Miyagawa Y, Okita H, Kiyokawa N, Akutsu H, Umezawa A, Matsunaga T (2013) Establishment and directed differentiation of induced pluripotent stem cells from glycogen storage disease type Ib patient. Genes Cells 18:1053–1069. https://doi.org/10.1111/gtc.12101
Si-Tayeb K, Noto FK, Nagaoka M, Li J, Battle MA, Duris C, North PE, Dalton S, Duncan SA (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51:297–305. https://doi.org/10.1002/hep.23354
Sun L, Wang Y, Cen J, Ma X, Cui L, Qiu Z, Zhang Z, Li H, Yang RZ, Wang C, Chen X, Wang L, Ye Y, Zhang H, Pan G, Kang JS, Ji Y, Zheng YW, Zheng S, Hui L (2019) Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes. Nat Cell Biol 21:1015–1026. https://doi.org/10.1038/s41556-019-0359-5
Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguchi H (2013) Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499:481–484. https://doi.org/10.1038/nature12271
Takebe T, Zhang RR, Koike H, Kimura M, Yoshizawa E, Enomura M, Koike N, Sekine K, Taniguchi H (2014) Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant. Nat Protoc 9:396–409. https://doi.org/10.1038/nprot.2014.020
Tannock IF, Hickman JA (2016) Limits to personalized cancer medicine. N Engl J Med 375:1289–1294. https://doi.org/10.1056/NEJMsb1607705
Torres-Duran M, Lopez-Campos JL, Barrecheguren M, Miravitlles M, Martinez-Delgado B, Castillo S, Escribano A, Baloira A, Navarro-Garcia MM, Pellicer D, Banuls L, Magallon M, Casas F, Dasi F (2018) Alpha-1 antitrypsin deficiency: outstanding questions and future directions. Orph J Rare Dis 13:114. https://doi.org/10.1186/s13023-018-0856-9
Touboul T, Hannan NR, Corbineau S, Martinez A, Martinet C, Branchereau S, Mainot S, Strick-Marchand H, Pedersen R, Di Santo J, Weber A, Vallier L (2010) Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology 51:1754–1765. https://doi.org/10.1002/hep.23506
Turnpenny PD, Ellard S (2012) Alagille syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet 20:251–257. https://doi.org/10.1038/ejhg.2011.181
Tuveson D, Clevers H (2019) Cancer modeling meets human organoid technology. Science 364:952–955. https://doi.org/10.1126/science.aaw6985
Velasco V, Shariati SA, Esfandyarpour R (2020) Microtechnology-based methods for organoid models. Microsyst Nanoeng 6:1–13. https://doi.org/10.1038/s41378-020-00185-3
Vyas D, Baptista PM, Brovold M, Moran E, Gaston B, Booth C, Samuel M, Atala A, Soker S (2018) Self-assembled liver organoids recapitulate hepatobiliary organogenesis in vitro. Hepatology 67:750–761. https://doi.org/10.1002/hep.29483
Wang S, Wang X, Tan Z, Su Y, Liu J, Chang M, Yan F, Chen J, Chen T, Li C, Hu J, Wang Y (2019) Human ESC-derived expandable hepatic organoids enable therapeutic liver repopulation and pathophysiological modeling of alcoholic liver injury. Cell Res 29:1009–1026. https://doi.org/10.1038/s41422-019-0242-8
Wang Y, Wang H, Deng P, Tao T, Liu H, Wu S, Chen W, Qin J (2020a) Modeling Human Nonalcoholic Fatty Liver Disease (NAFLD) with an Organoids-on-a-Chip System. ACS Biomater Sci Eng 6:5734–5743. https://doi.org/10.1021/acsbiomaterials.0c00682
Wang Z, He X, Qiao H, Chen P (2020b) Global trends of organoid and organ-on-a-chip in the past decade: a bibliometric and comparative study. Tissue Eng Part A 26:656–671. https://doi.org/10.1089/ten.TEA.2019.0251
Wu F, Wu D, Ren Y, Huang Y, Feng B, Zhao N, Zhang T, Chen X, Chen S, Xu A (2019) Generation of hepatobiliary organoids from human induced pluripotent stem cells. J Hepatol 70:1145–1158. https://doi.org/10.1016/j.jhep.2018.12.028
Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W (2012) Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife 1:e00049. https://doi.org/10.7554/eLife.00049
Zhang S, Chen S, Li W, Guo X, Zhao P, Xu J, Chen Y, Pan Q, Liu X, Zychlinski D (2011) Rescue of ATP7B function in hepatocyte-like cells from Wilson’s disease induced pluripotent stem cells using gene therapy or the chaperone drug curcumin. Hum Mol Genet 20:3176–3187. https://doi.org/10.1093/hmg/ddr223
Zheng F, Xiao Y, Liu H, Fan Y, Dao M (2021) Patient-specific organoid and organ-on-a-chip: 3D cell-culture meets 3D printing and numerical simulation. Adv Biol. https://doi.org/10.1002/adbi.202000024
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This work was supported by the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM4722223); by a grant (22213MFDS386) from Ministry of Food and Drug Safety in 2022; by the National Research Foundation (NRF) grant funded by the Korean government (MSIT) (NRF- 2022R1A2B5B02001644); and by the Technology Innovation Program (20009774) funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea).
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Lee, J., Mun, S.J., Shin, Y. et al. Advances in liver organoids: model systems for liver disease. Arch. Pharm. Res. 45, 390–400 (2022). https://doi.org/10.1007/s12272-022-01390-6
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DOI: https://doi.org/10.1007/s12272-022-01390-6