Regional Differences in Human Biliary Tissues and Corresponding In Vitro–Derived Organoids
Open accessAbstract
Background and Aims: Organoids provide a powerful system to study epithelia in vitro. Recently, this approach was applied successfully to the biliary tree, a series of ductular tissues responsible for the drainage of bile and pancreatic secretions. More precisely, organoids have been derived from ductal tissue located outside (extrahepatic bile ducts; EHBDs) or inside the liver (intrahepatic bile ducts; IHBDs). These organoids share many characteristics, including expression of cholangiocyte markers such as keratin (KRT) 19. However, the relationship between these organoids and their tissues of origin, and to each other, is largely unknown. Approach and Results: Organoids were derived from human gallbladder, common bile duct, pancreatic duct, and IHBDs using culture conditions promoting WNT signaling. The resulting IHBD and EHBD organoids expressed stem/progenitor markers leucine‐rich repeat–containing G‐protein‐coupled receptor 5/prominin 1 and ductal markers KRT19/KRT7. However, RNA sequencing revealed that organoids conserve only a limited number of regional‐specific markers corresponding to their location of origin. Of particular interest, down‐regulation of biliary markers and up‐regulation of cell‐cycle genes were observed in organoids. IHBD and EHBD organoids diverged in their response to WNT signaling, and only IHBDs were able to express a low level of hepatocyte markers under differentiation conditions. Conclusions: Taken together, our results demonstrate that differences exist not only between extrahepatic biliary organoids and their tissue of origin, but also between IHBD and EHBD organoids. This information may help to understand the tissue specificity of cholangiopathies and also to identify targets for therapeutic development.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Significant differences in morphology, functionality, or organoid formation efficiency depend on the cells-of-origin, different cells in the organoid, and medium composition.
“Significant differences in morphology and functionality or even organoid formation efficiency depend on the different cells-of-origin of the culture or different cells in the organoid as well as different medium composition120,202–204.”
From Organoids (2022) · cites this paper as [203]
The Results sections on intrahepatic bile duct organoids and extrahepatic organoid derivation report morphological differences between intra- and extrahepatic organoids and a change in single-cell organoid formation when medium components were removed. The hepatocyte-differentiation Results also report a functional difference. But the paper does not establish that differences among cell types within an organoid drive these outcomes, and it reports similar morphology and formation capacity across the three extrahepatic tissue origins. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThese organoids exhibited transcriptomic and phenotypic differences between cholangiocytes of different origin within the biliary tree.
“These organoids exhibited transcriptomic and phenotypic differences between cholangiocytes of different origin within the biliary tree [254].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [254]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Organoid Models and Applications in Biomedical Research
Xinaris, C., Brizi, V., & Remuzzi, G. (2015) · The Nephron journals/Nephron journals · doi:10.1159/000433566 · Cited by 3,517 · see citing works
Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M. M. A., Ellis, E., van Wenum, M., Fuchs, S. A., de Ligt, J., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.050 · Cited by 1,619 · see citing works
In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration
Huch, M., Dorrell, C., Boj, S. F., van Es, J. H., Li, V. S. W., van de Wetering, M., Sato, T., Hamer, K., Sasaki, N., Finegold, M. J., et al. (2013) · Nature · doi:10.1038/nature11826 · Cited by 1,555 · see citing works
A human liver cell atlas reveals heterogeneity and epithelial progenitors
Aizarani, N., Saviano, A., Sagar, Mailly, L., Durand, S., Herman, J. S., Pessaux, P., Baumert, T. F., & Grün, D. (2019) · Nature · doi:10.1038/s41586-019-1373-2 · Cited by 1,147 · see citing works
Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training
Roberts, C. K., Hevener, A. L., & Barnard, R. J. (2012) · Comprehensive physiology · doi:10.1002/cphy.c110062 · Cited by 919 · see citing works
Broutier, L., Andersson-Rolf, A., Hindley, C. J., Boj, S. F., Clevers, H., Koo, B.-K., & Huch, M. (2016) · Nature Protocols · doi:10.1038/nprot.2016.097 · Cited by 834 · see citing works
The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent ‘+4’ cell markers
Muñoz, J., Stange, D. E., Schepers, A. G., van de Wetering, M., Koo, B., Itzkovitz, S., Volckmann, R., Kung, K. S., Köster, J., Radulescu, S., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.166 · Cited by 758 · see citing works
Boulter, L., Govaere, O., Bird, T. G., Radulescu, S., Ramachandran, P., Pellicoro, A., Ridgway, R. A., Seo, S. S., Spee, B., Van Rooijen, N., et al. (2012) · Nature Medicine · doi:10.1038/nm.2667 · Cited by 747 · see citing works
Self-citationCholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration
Raven, A., Lu, W.-Y., Man, T. Y., Ferreira-Gonzalez, S., O’Duibhir, E., Dwyer, B. J., Thomson, J. P., Meehan, R. R., Bogorad, R., Koteliansky, V., et al. (2017) · Nature · doi:10.1038/nature23015 · Cited by 533 · see citing works
Self-citationCardinale, V., Wang, Y.-F., Carpino, G., Cui, C.-B., Gatto, M., Rossi, M., Berloco, P. B., Cantafora, A., Wauthier, E., Furth, M., et al. (2011) · Hepatology · doi:10.1002/hep.24590 · Cited by 348 · see citing works
Sampaziotis, F., Justin, A. W., Tysoe, O. C., Sawiak, S., Godfrey, E. M., Upponi, S. S., Gieseck, R. L., de Brito, M. C., Berntsen, N. L., Gómez-Vázquez, M. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4360 · Cited by 296 · see citing works
Self-citationPepe-Mooney, B. J., Dill, M. T., Alemany, A., Ordovas-Montanes, J., Matsushita, Y., Rao, A., Sen, A., Miyazaki, M., Anakk, S., Dawson, P. A., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.04.004 · Cited by 266 · see citing works
Tabibian, J. H., Masyuk, A. I., Masyuk, T. V., O'Hara, S. P., & LaRusso, N. F. (2013) · Comprehensive Physiology · doi:10.1002/cphy.c120019 · Cited by 240 · see citing works
Morphological, molecular, and functional heterogeneity of cholangiocytes from normal rat liver
Alpini, G. D., Roberts, S. K., Kuntz, S., Ueno, Y., Gubba, S., Podila, P. V., LeSage, G., & LaRusso, N. F. (1996) · Gastroenterology · doi:10.1053/gast.1996.v110.pm8613073 · Cited by 236 · see citing works
Planas-Paz, L., Sun, T., Pikiolek, M., Cochran, N. R., Bergling, S., Orsini, V., Yang, Z., Sigoillot, F., Jetzer, J., Syed, M., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.04.005 · Cited by 216 · see citing works
Hedgehog signaling maintains resident hepatic progenitors throughout life
Sicklick, J. K., Li, Y.-X., Melhem, A., Schmelzer, E., Zdanowicz, M., Huang, J., Caballero, M., Fair, J. H., Ludlow, J. W., McClelland, R., et al. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00456.2005 · Cited by 212 · see citing works
Kraiczy, J., Nayak, K., Howell, K. J., Ross, A., Forbester, J. L., Salvestrini, C., Mustata, R. C., Perkins, S., Andersson-Rolf, A., Leenen, E., et al. (2017) · Gut · doi:10.1136/gutjnl-2017-314817 · Cited by 180 · see citing works
Self-citationParacrine cellular senescence exacerbates biliary injury and impairs regeneration
Ferreira-Gonzalez, S., Lu, W.-Y., Raven, A., Dwyer, B., Man, T. Y., O’Duibhir, E., Lewis, P. J. S., Campana, L., Kendall, T. J., Bird, T. G., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03299-5 · Cited by 161 · see citing works
Self-citationCurrent management of biliary atresia
Kelly, D., & Davenport, M. (2007) · Archives of Disease in Childhood · doi:10.1136/adc.2006.101451 · Cited by 151 · see citing works
Morphological and functional heterogeneity of the mouse intrahepatic biliary epithelium
Glaser, S. S., Gaudio, E., Rao, A., Pierce, L. M., Onori, P., Franchitto, A., Francis, H., Dostal, D. E., Venter, J. K., DeMorrow, S., et al. (2009) · Laboratory Investigation · doi:10.1038/labinvest.2009.6 · Cited by 138 · see citing works
Tysoe, O., Justin, A. W., Brevini, T., Chen, S. E., Mahbubani, K. T. A., Frank, A. K., Zedira, H., Melum, E., Saeb‐Parsy, K., Markaki, A. E., et al. (2019) · Nature Protocols · doi:10.1038/s41596-019-0168-0 · Cited by 120 · see citing works
Self-citationMolecular mechanisms of bile duct development
Zong, Y., & Stanger, B. Z. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.06.020 · Cited by 95 · see citing works
Etiopathogenesis of primary sclerosing cholangitis
Chapman, R. W., & Cullen, S. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.3350 · Cited by 86 · see citing works
R‐spondin 1 and noggin facilitate expansion of resident stem cells from non‐damaged gallbladders
Lugli, N., Kamileri, I., Keogh, A., Malinka, T., Sarris, M. E., Talianidis, I., Schaad, O., Candinas, D., Stroka, D., & Halazonetis, T. D. (2016) · EMBO Reports · doi:10.15252/embr.201642169 · Cited by 74 · see citing works
Surgical anatomy of the biliary tract
Castaing, D. (2008) · HPB · doi:10.1080/13651820801992518 · Cited by 68 · see citing works
Evidence for multipotent endodermal stem/progenitor cell populations in human gallbladder
Carpino, G., Cardinale, V., Gentile, R., Onori, P., Semeraro, R., Franchitto, A., Wang, Y., Bosco, D., Iossa, A., Napoletano, C., et al. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.01.026 · Cited by 66 · see citing works
Karimian, N. G., den Dries, S. O., & Porte, R. J. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.02.023 · Cited by 51 · see citing works
Wilson, D. H., Jarman, E. J., Mellin, R., Wilson, M. L., Waddell, S. H., Tsokkou, P., Younger, N. T., Raven, A., Bhalla, S. R., Noll, A. T. R., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14283-3 · Cited by 47 · see citing works
Defining the human gallbladder proteome by transcriptomics and affinity proteomics
Kampf, C., Mardinoğlu, A., Fagerberg, L., Hallström, B. M., Danielsson, A., Nielsen, J., Pontén, F., & Uhlén, M. (2014) · PROTEOMICS · doi:10.1002/pmic.201400201 · Cited by 22 · see citing works
A Transcriptomic Signature of Mouse Liver Progenitor Cells
Passman, A. M., Low, J., London, R. M., Tirnitz‐Parker, J. E. E., Miyajima, A., Tanaka, M., Strick‐Marchand, H., Darlington, G., Finch‐Edmondson, M., Ochsner, S. A., et al. (2016) · Stem Cells International · doi:10.1155/2016/5702873 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Zhao, Z., Chen, X., Dowbaj, A. M., Sljukic, A., Bratlie, K., Lin, L., Fong, E. L. S., Balachander, G. M., Chen, Z., Soragni, A., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00174-y · Cited by 1,001 · see citing works
Cholangiocyte organoids can repair bile ducts after transplantation in the human liver
Sampaziotis, F., Muraro, D., Tysoe, O. C., Sawiak, S., Beach, T. E., Godfrey, E. M., Upponi, S. S., Brevini, T., Wesley, B. T., Garcia-Bernardo, J., et al. (2021) · Science · doi:10.1126/science.aaz6964 · Cited by 394 · see citing works
Self-citationBuilding consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids
Marsee, A., Roos, F. J. M., Verstegen, M. M. A., Marsee, A., Roos, F., Verstegen, M., Clevers, H., Vallier, L., Takebe, T., Huch, M., et al. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.04.005 · Cited by 310 · see citing works
Self-citationOrganoids in gastrointestinal diseases: From experimental models to clinical translation
Günther, C., Winner, B., Neurath, M. F., & Stappenbeck, T. S. (2022) · Gut · doi:10.1136/gutjnl-2021-326560 · Cited by 145 · see citing works
Biliary Atresia – emerging diagnostic and therapy opportunities
Lendahl, U., Lui, V. C. H., Chung, B., & Tam, P. K. H. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103689 · Cited by 117 · see citing works
Willemse, J., van Tienderen, G., van Hengel, E., Schurink, I., van der Ven, D., Kan, Y., de Ruiter, P., Rosmark, O., Westergren-Thorsson G, G., Schneeberger, K., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121473 · Cited by 106 · see citing works
Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia
Amarachintha, S. P., Mourya, R., Ayabe, H., Yang, L., Luo, Z., Li, X., Thanekar, U., Shivakumar, P., & Bezerra, J. A. (2022) · Hepatology · doi:10.1002/hep.32107 · Cited by 98 · see citing works
Verstegen, M. M. A., Roos, F. J. M., Burka, K., Gehart, H., Jager, M., de Wolf, M., Bijvelds, M. J. C., de Jonge, H. R., Ardisasmita, A. I., van Huizen, N. A., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-79082-8 · Cited by 86 · see citing works
Patient‐derived organoids for personalized gallbladder cancer modelling and drug screening
Yuan, B., Zhao, X., Wang, X., Liu, E., Liu, C., Zong, Y., Jiang, Y., Hou, M., Chen, Y., Chen, L., et al. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.678 · Cited by 81 · see citing works
Human branching cholangiocyte organoids recapitulate functional bile duct formation
Roos, F. J. M., van Tienderen, G. S., Wu, H., Bordeu, I., Vinke, D., Albarinos, L. M., Monfils, K., Niesten, S., Smits, R., Willemse, J., et al. (2022) · Cell stem cell · doi:10.1016/j.stem.2022.04.011 · Cited by 73 · see citing works
Self-citationOrganoids and Spheroids as Models for Studying Cholestatic Liver Injury and Cholangiocarcinoma
Sato, K., Zhang, W., Safarikia, S., Isidan, A., Chen, A. M., Li, P., Francis, H., Kennedy, L. L., Baiocchi, L., Alvaro, D., et al. (2020) · Hepatology · doi:10.1002/hep.31653 · Cited by 70 · see citing works
Human liver organoids: From generation to applications
Afonso, M. B., Marques, V., van Mil, S. W. C., & Rodrigues, C. M. P. (2024) · Hepatology · doi:10.1097/hep.0000000000000343 · Cited by 61 · see citing works
Hepatocyte organoids and cell transplantation: What the future holds
Peng, W. C., Kraaier, L. J., & Kluiver, T. A. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00579-x · Cited by 59 · see citing works
Roos, F. J. M., Wu, H., Willemse, J., Lieshout, R., Albarinos, L. A. M., Kan, Y., Poley, J., Bruno, M. J., de Jonge, J., Bártfai, R., et al. (2021) · Clinical and Translational Medicine · doi:10.1002/ctm2.566 · Cited by 40 · see citing works
Shi, S., Verstegen, M. M. A., Roest, H. P., Ardisasmita, A. I., Cao, W., Roos, F. J. M., de Ruiter, P. E., Niemeijer, M., Pan, Q., IJzermans, J. N. M., et al. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.10.009 · Cited by 38 · see citing works
Ardisasmita, A. I., Schene, I. F., Joore, I. P., Kok, G., Hendriks, D. F. G., Artegiani, B., Mokrý, M., Nieuwenhuis, E. E. S., & Fuchs, S. A. (2022) · Communications Biology · doi:10.1038/s42003-022-04046-9 · Cited by 37 · see citing works
Willemse, J., Roos, F. J. M., Voogt, I. J., Schurink, I. J., Bijvelds, M., de Jonge, H. R., van der Laan, L. J. W., de Jonge, J., & Verstegen, M. M. A. (2021) · Biotechnology and Bioengineering · doi:10.1002/bit.27613 · Cited by 35 · see citing works
Rezvani, M., Vallier, L., & Guillot, A. (2023) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2023.01.014 · Cited by 34 · see citing works
Self-citationHussein, K. H., Ahmadzada, B., Correa, J. C., Sultan, A., Wilken, S., Amiot, B., & Nyberg, S. L. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.06.001 · Cited by 28 · see citing works
“These organoids exhibited transcriptomic and phenotypic differences between cholangiocytes of different origin within the biliary tree [254].”
BackgroundEpigenetic Regulation of Cell-Fate Changes That Determine Adult Liver Regeneration After Injury
Aloia, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.643055 · Cited by 25 · see citing works
Willemse, J., van der Laan, L. J. W., de Jonge, J., & Verstegen, M. M. A. (2022) · Bioengineering · doi:10.3390/bioengineering9030110 · Cited by 26 · see citing works
Wang, L., Koui, Y., Kanegae, K., Kido, T., Tamura-Nakano, M., Yabe, S., Tai, K., Nakajima, Y., Kusuhara, H., Sakai, Y., et al. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122621 · Cited by 25 · see citing works
Artificial Intelligence for Organoids Multidimensional Assessment
Mo, Y., Wang, J., Yang, H., Bai, L., Xu, K., & Su, J. (2025) · SmartMat · doi:10.1002/smm2.70016 · Cited by 25 · see citing works
Roos, F. J. M., Verstegen, M. M. A., Albarinos, L. M., Roest, H. P., Poley, J., Tetteroo, G. W. M., IJzermans, J. N. M., & van der Laan, L. J. W. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.630492 · Cited by 25 · see citing works
Cell transplantation-based regenerative medicine in liver diseases
Cardinale, V., Lanthier, N., Baptista, P. M., Carpino, G., Carnevale, G., Orlando, G., Angelico, R., Manzia, T. M., Schuppan, D., Pinzani, M., et al. (2023) · Stem Cell Reports · doi:10.1016/j.stemcr.2023.06.005 · Cited by 27 · see citing works
Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver grafts
Tomofuji, K., Fukumitsu, K., Kondo, J., Horie, H., Makino, K., Wakama, S., Ito, T., Oshima, Y., Ogiso, S., Ishii, T., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121614 · Cited by 24 · see citing works
Chen, Y., Liu, Y., Chen, S., Zhang, L., Rao, J., Lu, X., & Ma, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1180184 · Cited by 24 · see citing works
Organoids for the Study of Liver Cancer
Wang, H., Calvisi, D. F., & Chen, X. (2021) · Seminars in Liver Disease · doi:10.1055/s-0040-1719176 · Cited by 21 · see citing works
Wu, P., Qiao, L., Yu, H., Ming, H., Liu, C., Wu, W., & Li, B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.758632 · Cited by 21 · see citing works
Regenerative medicine technologies applied to transplant medicine. An update
Petrosyan, A., Montali, F., Peloso, A., Citro, A., Byers, L. N., Pointe, C. L., Suleiman, M., Marchetti, A., McNeill, E. P., Speer, A. L., et al. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1015628 · Cited by 22 · see citing works
Han, D., Xu, K., Jin, Z., Xu, Y., Li, Y., Wang, L., Cao, Q., Kim, K.-P., Ryu, D. H., Hong, K., et al. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.85145 · Cited by 21 · see citing works
Single-cell transcriptomics identifies chondrocyte differentiation dynamics in vivo and in vitro
Lawrence, J. E. G., Woods Jon, S., Roberts, K., Sumanaweera, D., Balogh, P., Li, T., Predeus, A. V., He, P., Polański, K., Prigmore, E., et al. (2025) · Developmental Cell · doi:10.1016/j.devcel.2025.06.031 · Cited by 19 · see citing works
Sox9EGFP Defines Biliary Epithelial Heterogeneity Downstream of Yap Activity
Tulasi, D. Y., Castaneda, D. M., Wager, K., Hogan, C. B., Alcedo, K. P., Raab, J. R., & Gracz, A. D. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.01.009 · Cited by 18 · see citing works
Chen, J., Ma, S., Yang, H., Liang, X., Yao, H., Guo, B., Chen, D., Jiang, J., Shi, D., Xin, J., et al. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.03.012 · Cited by 20 · see citing works
Advances in liver organoids: model systems for liver disease
Lee, J., Mun, S. J., Shin, Y., Lee, S., & Son, M. J. (2022) · Archives of Pharmacal Research · doi:10.1007/s12272-022-01390-6 · Cited by 21 · see citing works
IL-17 signaling in primary sclerosing cholangitis patient-derived organoids
Moreno, A. S. G., Guicciardi, M. E., Wixom, A. Q., Jessen, E., Yang, J., Ilyas, S. I., Bianchi, J. K., Vairo, F. P. E., Lazaridis, K. N., & Gores, G. J. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000454 · Cited by 19 · see citing works
Liu, C., Wang, X., Liu, E., Zong, Y., Yu, W., Jiang, Y., Chen, J., Gu, M., Meng, Z., Li, J., et al. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01716-z · Cited by 19 · see citing works
Welch, N., Singh, S. S., Kumar, A., Dhruba, S. R., Mishra, S., Sekar, J., Bellar, A., Attaway, A. H., Chelluboyina, A., Willard, B. B., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101023 · Cited by 17 · see citing works
Distinct EpCAM-Positive Stem Cell Niches Are Engaged in Chronic and Neoplastic Liver Diseases
Safarikia, S., Carpino, G., Overi, D., Cardinale, V., Venere, R., Franchitto, A., Onori, P., Alvaro, D., & Gaudio, E. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00479 · Cited by 16 · see citing works
Efficient Establishment of Bile-Derived Organoids From Biliary Cancer Patients
Kinoshita, K., Tsukamoto, Y., Hirashita, Y., Fuchino, T., Kurogi, S., Uchida, T., Nakada, C., Matsumoto, T., Okamoto, K., Motomura, M., et al. (2023) · Laboratory Investigation · doi:10.1016/j.labinv.2023.100105 · Cited by 16 · see citing works
Impact of hypoxia and AMPK on CFTR-mediated bicarbonate secretion in human cholangiocyte organoids
Roos, F. J. M., Bijvelds, M. J. C., Verstegen, M. M. A., Roest, H. P., Metselaar, H. J., Polak, W. G., de Jonge, H. R., IJzermans, J. N. M., & van der Laan, L. J. W. (2021) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00389.2020 · Cited by 15 · see citing works
Frank, A. K., Chung, B. K., De Novales, M. L. L., Engesæter, L. K., Hoyle, H. W., Øgaard, J., Heslop, J., Karlsen, T. H., Tysoe, O., Brevini, T., et al. (2024) · Digestive Diseases and Sciences · doi:10.1007/s10620-024-08570-y · Cited by 14 · see citing works
Self-citationLou, C., Lan, T., Xu, S., Hu, X., Li, J., Xiang, Z., Lin, S., Fan, X., Chen, J., & Xu, X. (2025) · Gut · doi:10.1136/gutjnl-2025-334763 · Cited by 15 · see citing works
Lehmann, V., Schene, I. F., Ardisasmita, A. I., Liv, N., Veenendaal, T., Klumperman, J., van der Doef, H. P. J., Verkade, H. J., Verstegen, M. M. A., van der Laan, L. J. W., et al. (2021) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12450 · Cited by 13 · see citing works
Wang, Y., Zhang, X., Wang, X., Zhang, N., Yu, Y., Gong, P., Zhang, X., Ma, Y., Li, X., & Li, J. (2023) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0011062 · Cited by 13 · see citing works
Bile Chemistry During Ex Situ Normothermic Liver Perfusion Does Not Always Predict Cholangiopathy
Watson, C. J. E., Gaurav, R., Swift, L., Fear, C., Allison, M., Upponi, S. S., Brais, R. J., & Butler, A. J. (2024) · Transplantation · doi:10.1097/tp.0000000000004944 · Cited by 13 · see citing works
Serum Dickkopf-1 in Combined with CA 19-9 as a Biomarker of Intrahepatic Cholangiocarcinoma
Kim, S.-Y., Lee, H., Bang, S.-M., Han, D. H., Hwang, H. K., Choi, G.-H., Chung, M. J., & Kim, S. U. (2021) · Cancers · doi:10.3390/cancers13081828 · Cited by 13 · see citing works
Directing Cholangiocyte Morphogenesis in Natural Biomaterial Scaffolds
Smith, Q., Bays, J., Li, L., Shareef, H., Chen, C. S., & Bhatia, S. N. (2021) · Advanced Science · doi:10.1002/advs.202102698 · Cited by 13 · see citing works
RETRACTED: Molecular insights into experimental models and therapeutics for cholestasis
Zhang, W., Wu, H., Luo, S., Lu, X., Tan, X., Li, W., Ma, X., & Efferth, T. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116594 · Cited by 12 · see citing works
RetractedNew insights into tuft cell formation: Implications for structure–function relationships
O’Leary, C. E., Ma, Z., Culpepper, T., Novak, S. W., & DelGiorno, K. E. (2022) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2022.102082 · Cited by 12 · see citing works
Toward Transplantation of Liver Organoids: From Biology and Ethics to Cost-effective Therapy
ten Dam, M. J. M., Frederix, G., ten Ham, R. M. T., van der Laan, L. J. W., & Schneeberger, K. (2023) · Transplantation · doi:10.1097/tp.0000000000004520 · Cited by 12 · see citing works
Lederer, A., Görrissen, N., Nguyen, T. T., Kreutz, C., Rasel, H., Bartsch, F., Lang, H., & Endres, K. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-024-06012-x · Cited by 11 · see citing works
Ayabe, H., DePasquale, E. A. K., Amarachintha, S. P., Mourya, R., Li, W., Nalluri, S., Fox, S. R., Konishi, K., Shivakumar, P., & Bezerra, J. A. (2025) · Nature Communications · doi:10.1038/s41467-025-61442-5 · Cited by 11 · see citing works
Krüger, M., Samsom, R., Oosterhoff, L. A., van Wolferen, M. E., Kooistra, H. S., Geijsen, N., Penning, L. C., Kock, L. M., Sainz‐Arnal, P., Baptista, P. M., et al. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17510 · Cited by 11 · see citing works
Iqbal, A., Hul, N. V., Belicová, L., Corbat, A. A., Hankeová, S., & Andersson, E. R. (2023) · Liver International · doi:10.1111/liv.15789 · Cited by 11 · see citing works
Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases
Durazzo, M., Ferro, A., Navarro‐Tableros, V., Gaido, A., Fornengo, P., Altruda, F., Romagnoli, R., Moestrup, S. K., Calvo, P. L., & Fagoonee, S. (2025) · Biomolecules · doi:10.3390/biom15010121 · Cited by 11 · see citing works
Kaur, I., Vasudevan, A., Sánchez‐Romero, N., Sanyal, A., Sharma, A., Hemati, H., Juneja, P., Sharma, A., Plá-Palacín, I., Rastogi, A., et al. (2024) · Journal of Materials Chemistry B · doi:10.1039/d4tb01503g · Cited by 9 · see citing works
From fatty hepatocytes to impaired bile flow: Matching model systems for liver biology and disease
Kunst, R. F., Niemeijer, M., van der Laan, L. J. W., Spee, B., & van de Graaf, S. F. J. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114173 · Cited by 9 · see citing works
Highly Efficient Methods to Culture Mouse Cholangiocytes and Small Intestine Organoids
Chen, W., Yao, Q., Wang, R., Fen, B., Chen, J., Xu, Y., Yu, J., Li, L., & Cao, H. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.907901 · Cited by 9 · see citing works
Pirenne, S., Manzano‐Núñez, F., Loriot, A. E., Cordi, S., Desmet, L., Aydın, S., Hubert, C., Toffoli, S., Limaye, N., Sempoux, C. L., et al. (2024) · BMC Cancer · doi:10.1186/s12885-024-12770-0 · Cited by 8 · see citing works
In vitro liver models for toxicological research
Fukunaga, I., & Takebe, T. (2025) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2025.101478 · Cited by 7 · see citing works
Shimizu, T., Miyoshi, M., Kakinuma, S., Tsuchiya, J., Yamane, D., Watakabe, K., Mochida, T., Inada, K., Yamada, K., Shinozaki, K., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115675 · Cited by 7 · see citing works
Advancing animal health and disease research in the lab with three‐dimensional cell culture systems
Smith, D. W., Price, D. R. G., Faber, M., Chapuis, A. F., & McNeilly, T. N. (2022) · Veterinary Record · doi:10.1002/vetr.1528 · Cited by 8 · see citing works
Bioengineering liver tissue by repopulation of decellularised scaffolds
Afzal, Z., & Huguet, E. (2023) · World Journal of Hepatology · doi:10.4254/wjh.v15.i2.151 · Cited by 6 · see citing works
Gallbladder cholangiocyte organoids
Dutta, A., Chowdhury, N., Chandra, S., Guha, P., Saha, V., & GuhaSarkar, D. (2025) · Biology of the Cell · doi:10.1111/boc.202400132 · Cited by 6 · see citing works
Lui, V. C. H. (2025) · World Journal of Pediatric Surgery · doi:10.1136/wjps-2025-001010 · Cited by 6 · see citing works
Galanakis, V., Gribben, C., Munteanu, A., Cagna, M., Roos, F. J. M., Bulgaru, C., Ciortuz, L., Allison, M., Mohorianu, I. I., & Vallier, L. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.09.021 · Cited by 7 · see citing works
Self-citationHuman liver cholangiocyte organoids capture the heterogeneity of in vivo liver ductal epithelium
Bregante, J., Don, F. K., Rost, F., Gohr, A., Belenguer, G., Baenke, F., Liabeuf, D., Pöche, J., Schafmayer, C., Wilsch‐Bräuninger, M., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2025.116786 · Cited by 6 · see citing works
Mastering Organoid Growth: A Complete Guide to Overcoming Methodological Challenges
Jiao, C., Karakaya, O. F., Dadgar, N., Wehrle, C. J., Massoud, Z., Hong, H., Fairchild, R. L., Leipzig, N. D., Aucejo, F., Ma, W. W., et al. (2026) · MedComm · doi:10.1002/mco2.70571 · Cited by 8 · see citing works
Aktaş, R. G., Karski, M., Issac, B., Sun, L., Rockowitz, S., Piotr Sliz, A., & Vakili, K. (2022) · Cells · doi:10.3390/cells11233797 · Cited by 6 · see citing works
Cholangiocyte organoids for disease, cancer, and regenerative medicine
Nagao, M., Fukuda, A., Kashima, H., Matsuyama, S., Iimori, K., Nakayama, S., Mizukoshi, K., Kawai, M., Yamakawa, G., Omatsu, M., et al. (2024) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2024.151472 · Cited by 6 · see citing works
Impact of gallbladder hypoplasia on hilar hepatic ducts in biliary atresia
Miyazaki, N., Takami, S., Uemura, M., Oiki, H., Takahashi, M., Kawashima, H., Kanamori, Y., Yoshioka, T., Kasahara, M., Nakazawa, A., et al. (2024) · Communications Medicine · doi:10.1038/s43856-024-00544-5 · Cited by 6 · see citing works
Patient-derived organoid models to decode liver pathophysiology
Dwyer, B. J., & Tirnitz‐Parker, J. E. E. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.07.019 · Cited by 5 · see citing works
Kreiner, P., Eggenhofer, E., Schneider, L., Rejas, C., Goetz, M., Bogovic, N., Brunner, S. M., Evert, K., Schlitt, H. J., Geissler, E. K., et al. (2024) · Transplant International · doi:10.3389/ti.2024.13212 · Cited by 6 · see citing works
Cholangiocyte Organoids in Liver Transplantation; a Comprehensive Review
Rejas, C., & Junger, H. H. G. (2024) · Transplant International · doi:10.3389/ti.2024.12708 · Cited by 5 · see citing works
Schurink, I. J., de Jonge, J., & van der Laan, L. J. W. (2021) · Transplantation · doi:10.1097/tp.0000000000003790 · Cited by 5 · see citing works
DiPietro, E., Bharath, N., Karski, M., Durfee, O., Sherman, M. S., Ma, Q., Sun, L., Farghli, A. R., Smith, C. J., Kycia, I., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-11028-4 · Cited by 4 · see citing works
Equine endometrial organoids preserve tissue structure and cycle-stage transcriptional identity
Verstraete, M., Kuijpers, F., Holl, W., Norris, J. K., van Heule, M., Martin‐Pelaez, S., Heard, C. R., Uribe‐Salazar, J. M., Armién, A. G., Conley, A. J., et al. (2025) · Biology of Reproduction · doi:10.1093/biolre/ioaf232 · Cited by 4 · see citing works
Recapitulating the liver niche in vitro
Yap, K. K., & Mitchell, G. M. (2022) · Advances in stem cells and their niches · doi:10.1016/bs.asn.2021.10.002 · Cited by 3 · see citing works
Li, Y., Liu, J., Guan, T., Zhang, Y., Cheng, Q., Liu, H., Liu, C., Luo, W., Chen, H., Chen, L., et al. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.1057327 · Cited by 4 · see citing works
Yu, Y., Wang, Z., Mo, D. H., Wang, Z., & Li, G. (2021) · Mathematical Biosciences & Engineering · doi:10.3934/mbe.2021088 · Cited by 4 · see citing works
Cellular Homeostasis and Repair in the Biliary Tree
Wang, W., Chen, D., Wang, J., & Wen, L. (2022) · Seminars in Liver Disease · doi:10.1055/a-1869-7714 · Cited by 4 · see citing works
Biliatresone and Biliary atresia – Disease modelling in C57BL/6J neonatesPreprint
Schmidt, H. C., Hagens, J., Schuppert, P., Appl, B., Raluy, L. P., Trochimiuk, M., Philippi, C., Li, Z., Reinshagen, K., & Tomuschat, C. (2023) · Research Square · doi:10.21203/rs.3.rs-2430941/v1 · Cited by 4 · see citing works
Biliary stem cells in health and cholangiopathies and cholangiocarcinoma
Cardinale, V., Paradiso, S., & Alvaro, D. (2024) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000001005 · Cited by 3 · see citing works
Calder, A. N., Peter, M. Q., Tobias, J. W., Zaki, N. H. M., Keeley, T. M., Frankel, T. L., Samuelson, L. C., & Razumilava, N. (2024) · JCI Insight · doi:10.1172/jci.insight.181857 · Cited by 3 · see citing works
EGFR activation in cholangiocytes promotes extrahepatic bile duct regeneration after injury
Calder, A. N., Sakaguchi, T., Peter, M., Tobias, J. W., Frankel, T. L., & Razumilava, N. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000804 · Cited by 3 · see citing works
The influence of tissue spatial geometry and functional organisation on liver regeneration
Aloia, L. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.09.011 · Cited by 3 · see citing works
Exploiting the plasticity of cholangiocytes to repair the biliary tree
Frau, C., & Vallier, L. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102257 · Cited by 2 · see citing works
Self-citationWani, S. I., Mir, T. A., Nakamura, M. M., Tsuchiya, T., Alzhrani, A., Iwanaga, S., Arai, K., Alshehri, E. A., Shamma, T., Obeid, D. A., et al. (2024) · Bioprinting · doi:10.1016/j.bprint.2024.e00355 · Cited by 2 · see citing works
Bile Duct Repair in Human Liver Grafts: Effective Cholangiocyte Organoid Engraftment and Plasticity
van der Laan, L. J. W., Roos, F. J. M., & Verstegen, M. M. A. (2021) · Hepatology · doi:10.1002/hep.31877 · Cited by 1 · see citing works
Recent advances in multicellular human liver models
Mun, S. J., Lee, J., Shin, Y., Eun, V., Ji, Y., & Son, M. J. (2022) · Organoid · doi:10.51335/organoid.2022.2.e26 · Cited by 1 · see citing works
Positive autoregulation of Sox17 is necessary for gallbladder and extrahepatic bile duct formation
Trinh, L. T., Finnel, R. R., Osipovich, A. B., Musselman, J. R. B., Sampson, L. L., Wright, C. V. E., & Magnuson, M. A. (2025) · Development · doi:10.1242/dev.203033 · Cited by 2 · see citing works
Huang, J., Xia, X., Luo, F., Qu, L., Feng, X. H., & Zheng, L. (2026) · Advanced Biotechnology · doi:10.1007/s44307-026-00121-y · Cited by 1 · see citing works
Ji, Q., Liu, X., Tang, R., Yang, J. H., Zeng, Y., Aimaier, R., Liu, X., Kardumyan, V. V., Solovieva, A. B., Li, Q., et al. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123351 · Cited by 1 · see citing works
Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver graftsPreprint
Tomofuji, K., Fukumitsu, K., Kondo, J., Horie, H., Makino, K., Wakama, S., Ito, T., Oshima, Y., Ogiso, S., Ishii, T., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.14.468338 · Cited by 1 · see citing works
Cell isolation and Organoid Culture from Mouse Liver and Small IntestinePreprint
Chen, W., Yao, Q., Wang, R., Xu, Y., Yu, J., Wu, J., Li, L., & Cao, H. (2021) · Research Square · doi:10.21203/rs.3.rs-673633/v1
Advanced therapies for congenital biliary tract malformation: From bench to bedside
Shao, Y., Yang, X., Chen, H., Lu, D., Huang, Y., & Xu, X. (2022) · iLiver · doi:10.1016/j.iliver.2022.08.003
Regenerative Strategies in Biliary Tree Development in Health and Disease
Sriskanthanathan, A., Avini, E., Scott, A., Avini, A., & Froghi, S. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15717-2.00089-5
Su, Y., Tang, H., Miao, X., Yu, C., Chai, C., Huang, W. B., Li, L., Zheng, J., Xu, T., Jin, F., et al. (2025) · Human Cell · doi:10.1007/s13577-025-01276-x
Biliary tree stem cell transplantation
Paradiso, S., Cremisini, F., Franchitto, M., Carpino, G., & Cardinale, V. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-823524-9.00014-9
- Authors
- Rimland, C. A., Tilson, S. G., Morell, C. M., Tomaz, R. A., Lu, W., Adams, S. E., Georgakopoulos, N., Otaizo‐Carrasquero, F., Myers, T. G., Ferdinand, J. R., Gieseck, R. L., Sampaziotis, F., Tysoe, O. C., Ross, A., Kraiczy, J. M., Wesley, B., Muraro, D., Zilbauer, M., Oniscu, G. C., Hannan, N. R. F., Forbes, S. J., Saeb‐Parsy, K., Wynn, T. A., & Vallier, L.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- National Institutes of Health (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- MRC Centre for Regenerative Medicine (GB)
- University of Cambridge (GB)
- Genomic Technologies Section,Research Technologies Branch,NIAID,NIH,Bethesda,MD
- Corresponding author
- Tilson, Samantha G.
- Morell, Carola M.
- Tomaz, Rute A.
- Vallier, Ludovic
- ORCID
- Rimland, Casey A.
- Tilson, Samantha G.
- Morell, Carola M.
- Tomaz, Rute A.
- Lu, Wei‐Yu
- Georgakopoulos, Nikitas
- Myers, Timothy G.
- Ferdinand, John R.
- Gieseck, Richard L.
- Sampaziotis, Fotios
- Tysoe, Olivia C.
- Ross, Alexander
- Kraiczy, Judith M.
- Wesley, Brandon
- Muraro, Daniele
- Zilbauer, Matthias
- Oniscu, Gabriel C.
- Hannan, Nicholas R.F.
- Forbes, Stuart J.
- Saeb‐Parsy, Kourosh
- Wynn, Thomas A.
- Vallier, Ludovic
- Venue
- Hepatology
- Published
- 2021-01
- Volume
- 73
- Issue
- 1
- Pages
- 247-267
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC8641381
- OpenAlex
- W3013894747
- Cited by
- 110
- References
- 30
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 18 · 2023: 13 · 2022: 19 · 2021: 23 · 2020: 5
- FWCI
- 8.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Hepatology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Bill and Melinda Gates Foundation (OPP1144)
- Wellcome Trust
- National Institute for Health and Care Research (CL-2017-14-001, OPP1144)
- Cystic Fibrosis Trust (VIA 028)
- Academy of Medical Sciences (SGL019\1071)
- Rosetrees Trust
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/R001987/1, NC/T2T0419, NC/N001540/1)
- Cambridge Trust
- Gates Cambridge Trust (#OPP1144)
- National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/N001540/1, NC/R001987/1)
- National Institutes of Health
- Medical Research Council (MR/T001917/1, MR/P016839/1, MC_PC_12009, OPP1144, MR/K017047/1, MC_PC_17230)
- Engineering and Physical Sciences Research Council (TS/H001220/1)
- NIHR Cambridge Biomedical Research Centre (OPP1144)
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- NHLBI Division of Intramural Research
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gallbladder and Bile Duct Disorders
- Keywords
- intrahepatic bile ducts, extrahepatic bile ducts, cholangiocytes, keratin 19, keratin 7, Wnt signaling, gallbladder, common bile duct, pancreatic duct, cholangiopathy, hepatocyte differentiation, cell cycle genes
- MeSH terms
- RNA-Seq, Animals, Bile, Bile Ducts, Intrahepatic, Cell Differentiation, Common Bile Duct, Epithelial Cells, Gallbladder, Gene Expression Regulation, Humans, Liver, Tissue and Organ Procurement, Organoids, Bile Ducts, Extrahepatic, Mice, Keratin-19
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
