The DOI matches its Crossref record; 67 of the 68 references it cites were found in a registry or an index.
Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids
Open accessAbstract
The mammalian liver possesses a remarkable regenerative ability. Two modes of damage response have been described: (1) The "oval cell" response emanates from the biliary tree when all hepatocytes are affected by chronic liver disease. (2) A massive, proliferative response of mature hepatocytes occurs upon acute liver damage such as partial hepatectomy (PHx). While the oval cell response has been captured in vitro by growing organoids from cholangiocytes, the hepatocyte proliferative response has not been recapitulated in culture. Here, we describe the establishment of a long-term 3D organoid culture system for mouse and human primary hepatocytes. Organoids can be established from single hepatocytes and grown for multiple months, while retaining key morphological, functional and gene expression features. Transcriptional profiles of the organoids resemble those of proliferating hepatocytes after PHx. Human hepatocyte organoids proliferate extensively after engraftment into mice and thus recapitulate the proliferative damage-response of hepatocytes.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the formation of organoids also recapitulate a 3D in vivo‐like microenvironment that may well compensate for the lack of structural support for tissue formation in the damaged extracellular matrix environment when used as xenografts.[ 18 , 19 ]”
From Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin (2021) · cites this paper as [19]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Hu et al. demonstrated that hepatocyte-derived organoids undergo an initial 30-day quiescent phase post-transplantation, succeeded by rapid and extensive liver repopulation akin to that of PHs [16].”
From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“We further demonstrate the versatility and flexibility of multiplexed CRISPR base-editing for cancer modeling across several epithelial tissues by mutating liver, endometrium, and organoids32–34.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [33]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Furtherly, functional intestinal organoids exhibit a relatively thick mucus layer due to mucus secretion from mature goblet cells122, which can be detected by Alcian blue (AB) and periodic acid-Schiff (PAS) staining123,124.”
From Organoids (2022) · cites this paper as [124]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2467 · Cited by 6,907
Sato, T., Stange, D. E., Ferrante, M., Vries, R. G. J., van Es, J. H., van den Brink, S., van Houdt, W. J., Pronk, A., van Gorp, J., Siersema, P. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.050 · Cited by 3,753
Self-citationMolecular cloning and expression of human hepatocyte growth factor
Nakamura, T., Nishizawa, T., Hagiya, M., Seki, T., Shimonishi, M., Sugimura, A., Tashiro, K., & Shimizu, S. (1989) · Nature · doi:10.1038/342440a0 · Cited by 2,158
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
Self-citationIn 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
Self-citationHuman primary liver cancer–derived organoid cultures for disease modeling and drug screening
Broutier, L., Mastrogiovanni, G., Verstegen, M. M., Francies, H. E., Gavarró, L. M., Bradshaw, C. R., Allen, G. E., Arnes-Benito, R., Sidorova, O., Gaspersz, M. P., et al. (2017) · Nature Medicine · doi:10.1038/nm.4438 · Cited by 1,471
Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells
Si-Tayeb, K., Noto, F. K., Nagaoka, M., Li, J., Battle, M. A., Duris, C., North, P. E., Dalton, S., & Duncan, S. A. (2010) · Hepatology · doi:10.1002/hep.23354 · Cited by 1,282
Single-cell messenger RNA sequencing reveals rare intestinal cell types
Grün, D., Lyubimova, A., Kester, L., Wiebrands, K., Basak, O., Sasaki, N., Clevers, H., & van Oudenaarden, A. (2015) · Nature · doi:10.1038/nature14966 · Cited by 1,234
Self-citationMicroscale culture of human liver cells for drug development
Khetani, S. R., & Bhatia, S. N. (2008) · Nature Biotechnology · doi:10.1038/nbt1361 · Cited by 1,219
Cited by
Sorted by citations
Items 501–600 of 839
Organoids for Modeling (Colorectal) Cancer in a Dish
Rathje, F., Klingler, S., & Aberger, F. (2022) · Cancers · doi:10.3390/cancers14215416 · Cited by 10
“In addition to mammary [13] and intestinal organoids, many other types of organoids cultivated from a variety of tissues and organs were described in the past years: organoids were established for stomach [14,15], liver [16,17], pancreas [18–20], kidney [21,22], prostate [23,24], ovaries [25,26], endometrium [27], eso…”
BackgroundOck, S. A., Kim, S.-Y., Ju, W. S., Kim, Y.-I., Wi, H., & Lee, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015429 · Cited by 8
“However, we successfully generated functional mature HOs by optimizing the cell seeding density of pig hepatocytes (20,000 hepatocytes/50 µ L Matrigel dome) based on the criteria reported in humans and mice [10].”
BackgroundMethodInfluentialIntestinal organoid technology and applications in probiotics
Tan, H., Chen, X., Wang, C., Song, J., Xu, J., Zhang, Y., & Suo, H. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2288887 · Cited by 9
“…as Helicobacter pylori infection (Bartfeld et al. 2015); liver organoids established in mice and humans to reflect regeneration after hepatectomy (Hu et al. 2018); human kidney organoids consisting of renal units, which are linked to the collecting duct network and surrounded by mesenchymal and…”
Zhou, J., Huang, Y., Wang, W., Li, J., Hou, Y., Yi, Z., Yang, H., Hu, K., Zhu, Y., Wang, Z., et al. (2024) · Advanced Science · doi:10.1002/advs.202305925 · Cited by 8
Self-citationChen, Y., Ku, Y.-H., Wang, K.-C., Chiang, H.-C., Hsu, Y.-P., Cheng, M.-T., Wang, C., & Wee, Y. (2022) · Gels · doi:10.3390/gels8030149 · Cited by 8
Genetic and Cellular Contributions to Liver RegenerationPreprint
Liang, R. J., Lin, Y.-H., & Zhu, H. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a040832 · Cited by 8
WITHDRAWN: In Vitro three-dimensional (3D) cell culture tools for spheroid and organoid models
Lee, S., Koo, I.-S., Hwang, H. J., & Lee, D. W. (2023) · SLAS DISCOVERY · doi:10.1016/j.slasd.2023.12.003 · Cited by 9
RetractedRen, J., Liu, M., Rong, M., Zhang, X., Wang, G., Liu, Y., Li, H., & Duan, S. (2024) · Cell organoid (Print) · doi:10.26599/co.2024.9410009 · Cited by 8
Biomedical applications of organoids in genetic diseases
Huang, W., Jeong, S., Kim, W., & Chen, L. (2024) · Medical Review · doi:10.1515/mr-2024-0077 · Cited by 7
Hepatobiliary organoid research: the progress and applications
Zou, R.-Q., Dai, Y.-S., Liu, F., Yang, S., Hu, H., & Li, F. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1473863 · Cited by 9
Self-citationIn 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
Insights into Modeling Inflammatory Bowel Disease from Stem Cell Derived Intestinal Organoids
Zhao, Q., Shao, M., Ma, L., & Zhou, R. (2025) · Stem Cell Reviews and Reports · doi:10.1007/s12015-025-10887-8 · Cited by 10
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 9
Immunocompatibility in transplantation: adapting to a changing therapeutic landscape
Güell-Alonso, R., Cabrera-Pérez, R., & Vives, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1648534 · Cited by 7
“Kidney and liver organoids mimicking native tissue architecture are also being developed to increase graft availability (61 – 63).”
Yang, X., Nie, Y., Lu, C., Li, Y., Hayashi, Y., Plummer, R., Luo, N., Li, Q., Kasai, T., Okumura, T., et al. (2025) · Developmental Cell · doi:10.1016/j.devcel.2025.09.002 · Cited by 11
Harnessing Next‐Generation 3D Cancer Models to Elucidate Tumor‐Microbiome Crosstalk
Buzhor, M. G., Longobardi, G., Kandli, O., Krinsky, A., Avramoff, O., Katyal, A., Salomon, K., Miari, A., Venkert, D., Barnatan, T. T., et al. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202503198 · Cited by 7
Patient-Derived Tumour Organoids (PDOs) may help oncologists in clinical practice
Brandi, R., Palcau, A. C., Migliano, E., Strano, S., & Blandino, G. (2025) · Personalized Medicine · doi:10.1080/17410541.2025.2581557 · Cited by 7
Organoids as platforms for infectious disease research
Liu, K., Zhao, Y., Joloya, E. M., Artegiani, B., Bartfeld, S., Choi, Y. K., Han, Y., Hendriks, D. F. G., Hoogduijn, M. J., Hudson, J. E., et al. (2026) · Nature Reviews Bioengineering · doi:10.1038/s44222-026-00445-3 · Cited by 7
“Furthermore, hepatocyte organoids derived from human fetal liver 83 can be applied to model infection by the Plasmodium parasite responsible for malaria (Fig.”
Self-citationHowell, L., Jenkins, R. E., Lynch, S., Duckworth, C., Kevin Park, B., & Goldring, C. (2021) · Archives of Toxicology · doi:10.1007/s00204-021-03075-3 · Cited by 7
Gong, Z., Mao, Y., Huang, L., Tang, X., Zhang, L., Xu, Y., Ding, Z., Zhao, X., Wang, F., & Guo, S. (2023) · Advanced Materials Technologies · doi:10.1002/admt.202201942 · Cited by 9
Kuboyama‐Sasaki, A., Takahashi, Y., Chen, X., Hiro, K., Kobayashi, T., Ohdan, H., Shimizu, M., Yamauchi, Y., Kiyono, H., & Sato, R. (2023) · Biotechnology Journal · doi:10.1002/biot.202300365 · Cited by 7
Babboni, S., Vacca, P. G., Simonini, L., Pezzati, D., Martinelli, C., Frongillo, F., Bianco, G., Marciano, E., Basta, G., Ghinolfi, D., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13061804 · Cited by 7
“Table 3 resumes these multifaceted issues and recommends measures that need to be taken to ensure the clinical application of this technology.”
BackgroundLiver and bile duct organoids and tumoroids
Luo, X., Gong, Y., Gong, Z., Fan, K., Suo, T., Liu, H., Ni, X., Ni, X., Abudureyimu, M., & Liu, H. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117104 · Cited by 7
Mice Engrafted with Human Liver Cells
de Jong, Y. P. (2024) · Seminars in Liver Disease · doi:10.1055/s-0044-1790601 · Cited by 9
“Liver chimeras have proven valuable for studying liver regeneration, as evidenced by research into hepatocyte ploidy, 131 fetal hepatoblast transplantation, and maturation, 32,132 and modeling the proliferation capacityof hepatocytes, as demonstrated by serial murine hepatocyte transplantation.”
Generation of new hepatocyte-like in vitro models better resembling human lipid metabolism
Pramfalk, C., Jakobsson, T., Verzijl, C. R. C., Minniti, M. E., Obensa, C., Ripamonti, F., Olin, M., Pedrelli, M., Eriksson, M., & Parini, P. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2020.158659 · Cited by 7
Cui, X., Han, L., Cui, L., Fu, G., Liu, E., Wang, D., Song, B., Zhang, Y., Zhou, W., Wang, H., et al. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106583 · Cited by 7
Wang, J., Situ, P., Chen, S., Wu, H., Zhang, X., Liu, S., Wang, Y., Xie, J., Chen, H., & Duan, Y. (2022) · Cells · doi:10.3390/cells11244117 · Cited by 7
Liver Organoid Potential Application for Hepatitis E Virus Infection
Xiang, K., & Zhuang, H. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-981-99-1304-6_9 · Cited by 7
The Progress and Promise of Lineage Reprogramming Strategies for Liver Regeneration
Wang, S., Wang, X., & Wang, Y. (2024) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2024.101395 · Cited by 7
“39,40 Despite using the same initial cells, such as primary mouse or human hepatocytes, organoid technology-derived expandable hepatic cells differ from chemical reprogramming-derived expandable hepatic cells.”
BackgroundMastering 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 9
“The transplantation of mouse [ 179 ] and human [ 180, 181 ] hepatocyte organoids, generated much more extensive engraftment.”
The promise and potential of liver organoids: Development, classification and application
Wang, Y., Ye, Z., Lin, Y., Zhao, Y., Zhong, D., Chen, J., Yin, J., Yan, J., & Wang, Y. (2026) · TransMed · doi:10.1016/j.tmed.2026.100003 · Cited by 6
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
Application of organoids in otolaryngology: head and neck surgery
Zhu, H., Qu, S., Deng, Y., Gong, M., Xiang, Y., Teng, Y., & Ye, D. (2023) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-023-08348-4 · Cited by 6
Hepatic organoids move from adolescence to maturity
Guan, Y., & Peltz, G. (2024) · Liver International · doi:10.1111/liv.15893 · Cited by 6
“4 They also developed CRISPR meth - odology for engineering the genome of the cells used to produce these organoids, which enabled the impact of various genes on liver phenotypes to be examined.”
BackgroundLi, P., Miyamoto, D., Fukumoto, M., Kawaguchi, Y., Yamashita, M., Tetsuo, H., Adachi, T., Hidaka, M., Hara, T., Soyama, A., et al. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03877-z · Cited by 6
“Although the induction of iPSCs into HBOs has many advantages, induced organoids are often immature and difficult to culture for long periods of time, which requires further research [38].”
BackgroundOrganoid as a promising tool for primary liver cancer research: a comprehensive review
Hu, X., Wei, J., Liu, P., Zheng, Q., Zhang, Y., Zhang, Q., Yao, J., & Ni, J. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01287-5 · Cited by 6
“…identified to be potentially beneficial to patients were HDAC inhibitors (romidep-sin and panobinostat), proteasome inhibitors (ixazomib, bortezomib, carfilzomib, and omacetaxel), DNA Top2 inhibitors (idarubicin, zorubicin, and tolteroderma), and inhibitors of RNA synthesis (procamycin) [39].”
BackgroundCholangiocyte 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 7
Zhou, X. Y., Liu, W., Sun, H., Peng, Y., Huang, R.-J., Chen, C., Zhang, H., Zhou, S.-A., Wu, H., Tang, D., et al. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000614 · Cited by 6
Dong, Y., Wang, J., Ji, W., Zheng, M., Wang, P., Liu, L., & Li, S. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.744969 · Cited by 6
Barhouse, P. S., Andrade, M. J., & Smith, Q. (2022) · Frontiers in Chemical Engineering · doi:10.3389/fceng.2022.832754 · Cited by 6
“Additionally, hepatocyte organoids formed transdifferentiated cystic structures under the right conditions and repopulated damaged liver when transplanted into a mouse model (Hu et al., 2018).”
BackgroundNarrative engineering of the liver
Lee, I. S., & Takebe, T. (2022) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2022.101925 · Cited by 6
Chi, K. Y., & Kim, J. (2022) · Organoid · doi:10.51335/organoid.2022.2.e6 · Cited by 6
“been generated by embedding primary human hepatocytes (PHHs) in Matrigel [43].”
BackgroundMethodInfluentialModeling Liver Development and Disease in a Dish
Iqbal, W., Wang, Y., Sun, P., & Zhou, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115921 · Cited by 6
“Subsequent studies have successfully generated organoids using PSCs and tissue-specific progenitor cells to model organs derived from the ectoderm, mesoderm, and endoderm [33] (Figure 2), including the liver [12,30,34,35] (Table 1).”
BackgroundInfluentialXu, R., Wu, J., Pan, J., Zhang, S., Yang, Y., Zhang, L., Zhou, W., Wu, N., Hu, D., Ji, G., et al. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1444561 · Cited by 6
“Primary hepatocytes were extracted from the liver of mice according to previous studies (Hu et al., 2018; Charni-Natan and Goldstein, 2020).”
MethodFounder cells for hepatocytes during liver regeneration: from identification to application
Wei, S., Tang, J., & Cai, X. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03457-3 · Cited by 6
Cancer Risk and Mutational Patterns Following Organ Transplantation
Shen, Y., Lian, D., Shi, K., Gao, Y., Hu, X., Yu, K., Zhao, Q., & Feng, C. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.956334 · Cited by 6
“In addition, the impaired immune detection function of tumor cells and the use of immunosuppressive agents are both key factors that induce tumors in organ recipients directly (Hunt, 2006).”
BackgroundSingle-Cell Resolution Three-Dimensional Imaging of Intact Organoids
van Ineveld, R. L., Ariese, H. C., Wehrens, E. J., Dekkers, J. F., & Rios, A. C. (2020) · Journal of Visualized Experiments · doi:10.3791/60709-v · Cited by 6
Self-citationRegenerative human liver organoids (HLOs) in a pillar/perfusion plate for hepatotoxicity assaysPreprint
Shrestha, S., Acharya, P., Kang, S. Y., Vanga, M. G., Lekkala, V. K. R., Liu, J., Yang, Y. S., Joshi, P., & Lee, M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.25.586638 · Cited by 5
“In 2018, Hu et al. 8 generated human hepatocyte organoids by the expansion of primary human hepatocytes.”
Inui, J., Ueyama-Toba, Y., Imamura, C., Nagai, W., Asano, R., & Mizuguchi, H. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123148 · Cited by 5
Hu, Y., Zhang, Z., Adiham, A., Li, H., Gu, J. H., & Gong, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020696 · Cited by 7
“By 2018, more mature and durable hepatocyte organoids were established from purified axis inhibition protein 2 (Axin2) mouse hepatocytes [112].”
IL-22 supports long-term expansion of mouse and human hepatocytes
Li, B., Guo, R., Wang, S., Zhang, J., Wang, S., Yuan, Q., Zheng, H., Wang, Y., Sun, B., Tang, E., et al. (2026) · Journal of Hepatology · doi:10.1016/j.jhep.2026.01.016 · Cited by 5
Microengineering the Liver: Strategies for Constructing Functional Liver‐on‐a‐Chip Devices
Wang, J., Liang, Z., Wang, J., Li, Z., Wang, S., Wei, Y., Xie, X., & Huang, D. (2026) · Exploration · doi:10.1002/exp2.70137 · Cited by 5
Organoids: technology refining, current applications and future directions
Cheng, X., Fang, Z., Sun, J., Liu, L., Yang, Y., Wang, J., Shuai, J., Zhou, X., Lin, P., Yang, G., et al. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00422-7 · Cited by 6
“Indeed, the feasibility of transplantation, in vivo functional engraftment, and regeneration of liver [91], colon [37, 92], and pancreas organoids [93] have been demonstrated in various mouse models.”
Cadherin-engineered microspheres enable scalable biofabrication of multilineage liver organoids
Qin, Z., Cao, L., Liu, C., 安永, Li, F., Yang, X., Chen, G., Qian, M., Zhang, Y., & Yang, J. (2026) · Trends in biotechnology · doi:10.1016/j.tibtech.2026.03.014 · Cited by 5
Yoon, Y., Kim, C. W., Kim, M. Y., Baik, S. K., Jung, P. Y., & Eom, Y. W. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021325 · Cited by 5
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
Goswami, Y., Baghel, A., Sharma, G., Sharma, P. K., Biswas, S., Yadav, R., Garg, P. K., Shalimar, S., & Tandon, R. (2024) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2024.102463 · Cited by 6
Recent progress in the identification and in vitro culture of skin organoids
Huang, Y., Ye, Q., Wang, J., Kaimin, Z., Yang, H., Jiang, X., & Shen, M. (2025) · Regenerative Therapy · doi:10.1016/j.reth.2025.01.001 · Cited by 8
Respiratory microphysiological system in respiratory research: recent advances and future prospects
Yin, J., Bi, Z., Dai, T., Zhu, X. A., Xu, T., & Liu, H. (2025) · Respiratory Research · doi:10.1186/s12931-025-03327-1 · Cited by 5
“Since then, numerous ASC-derived organoids have been successfully established [89–91].”
Liver regeneration: metabolic and epigenetic regulation
Verma, S., Purohit, J. S., Arora, A., Sinha, S., & Chaturvedi, M. M. (2021) · Hepatoma Research · doi:10.20517/2394-5079.2020.122 · Cited by 5
“Recently, long-term three dimensional organoid culture systems for hepatocytes and cholangiocytes from mice and humans have also been established, which recapitulate morphological, functional and transcriptional features of liver regeneration([10]).”
BackgroundRole of Biliary Organoids in Cholestasis Research and Regenerative Medicine
Soroka, C. J., Roberts, S. J., Boyer, J. L., & Assis, D. N. (2021) · Seminars in Liver Disease · doi:10.1055/s-0041-1728663 · Cited by 5
Transforming one organ into another to overcome challenges in tissue engineering
Wang, Z., Tian, X., Wang, C., Qi, X., Gracia‐Sancho, J., & Dong, L. (2022) · Portal hypertension & cirrhosis · doi:10.1002/poh2.26 · Cited by 5
A hepatoprotective role of peritumoral non-parenchymal cells in early liver tumorigenesis
Tian, C. L., Li, L., Fan, L., Brown, A. R., Norris, E. J., Morrison, M., Glazer, E. S., & Zhu, L. (2023) · Disease Models & Mechanisms · doi:10.1242/dmm.049750 · Cited by 6
“The same culture medium was used for all spheroid cultures: 50% mouse HepatiCult ™ Organoid Growth Medium (STEMCELL Technologies), 50% cholangiocyte organoid culture medium reported previously (Hu et al., 2018) and 1% Matrigel.”
An Exploration of Organoid Technology: Present Advancements, Applications, and Obstacles
Mishra, I., Gupta, K., Mishra, R., Chaudhary, K., & Sharma, V. (2023) · Current Pharmaceutical Biotechnology · doi:10.2174/0113892010273024230925075231 · Cited by 5
Xu, Z.-Y., Wang, M., Shi, J.-Y., Liu, Y., Yu, C., Zhang, X.-Y., Zhang, C.-W., He, Q.-F., Pan, C., Zhou, J., et al. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.101700 · Cited by 5
“The perfusion solutions were prepared as described [4,5].”
InfluentialQin, S., Bo, X., Liu, H., Zhang, Z., Zhao, Z., & Xia, Q. (2025) · Hepatology · doi:10.1097/hep.0000000000001321 · Cited by 6
Lian, J., An, Y., Wei, W., Lu, Y., Zhang, X., Sun, G., Guo, H., Xu, L., Chen, X., & Hu, H. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115633 · Cited by 5
Self-citationAnalysis of the mechanism underlying liver diseases using human induced pluripotent stem cells
Kakinuma, S., & Watanabe, M. (2019) · Immunological Medicine · doi:10.1080/25785826.2019.1657254 · Cited by 6
Zhang, W., Xu, Y., Wang, X., Oikawa, T., Su, G., Wauthier, E., Wu, G., Sethupathy, P., He, Z., Liu, J., et al. (2023) · Matrix Biology · doi:10.1016/j.matbio.2023.06.008 · Cited by 5
Current stem cells technologies used in medicine
Müller, M., Czarnecka, J., Brzeziński, M., Prus, J., Kulak, B., Hołubowski, A., Stasiak, M., Borowiec, B. M., Bryl, R., Moncrieff, L., et al. (2020) · Medical Journal of Cell Biology · doi:10.2478/acb-2020-0016 · Cited by 5
“The possibility of observing hepatocytes proliferation and regeneration in vitro allows for a better understanding of hepatic diseases and liver participation in detoxification [46].”
BackgroundHabil, M. R., Salazar‐González, R. A., Doll, M. A., & Hein, D. W. (2022) · Archives of Toxicology · doi:10.1007/s00204-022-03381-4 · Cited by 5
Rezvani, M., Lewis, K., Quach, S., Iwasawa, K., Weihs, J., Reza, H. A., Cai, Y., Kimura, M., Zhang, R., Milton, Y., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.11.617794 · Cited by 5
Rao, S., Romal, S., Torenvliet, B., Slotman, J. A., Huijs, T. T. G., & Mahmoudi, T. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e30740 · Cited by 4
The Use of Organoid Cultures in Advancing Nutrition Research
Menikdiwela, K. R., Lenis, M., & Storch, J. (2025) · Advances in Nutrition · doi:10.1016/j.advnut.2025.100489 · Cited by 4
“…cultures, including milk production in mammary gland organoids, glycogen accumulation and protein expression in liver organoids, and advanced intestinal organoids [105 ‒ 107], none of these orga-noid systems are yet capable of reproducing full functional organs with a complete maturity [20].”
Flow cytometry protocol for cell death analysis in glioblastoma organoids: A technical note
Potthoff, A., Hsieh, M., Melhem, A., Ng, S. S., Pregler, B. E. F., Vieregge, A., Raspe, M., Friker, L. L., Zeyen, T., Layer, J. P., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0327660 · Cited by 4
“The versatility of organoids is evident from their utilization across a broad spectrum of cancer entities [3], including lung, breast, liver, and intestinal cancers [6,7,9,10] as well as tumors of the central nervous system (CNS), like meningioma or glioblastoma [11–14].”
Wu, H., Wang, J., Liu, S., Wang, Y., Xie, J., Zhang, X., Zhang, S., Gu, W., Zhou, Y., & Duan, Y. (2025) · Biomaterials Research · doi:10.34133/bmr.0280 · Cited by 4
“These include hepatocyte organoids [ 2 ], cholangiocyte organoids [ 3 ], hepatobiliary organoids [ 4 ], and multilineage hepatic organoids [ 5 ].”
Cartilage organoids: an emerging platform for novel osteoarthritis therapies
Gao, B., Chen, Z., Long, Y., He, F., Gan, D., Yi, W., Xiao, G., Ren, J., & Qin, L. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1668766 · Cited by 7
“Organoids are self-assembling 3D tissues generated from pluripotent stem cells or adult cells, which have been recognized as a emerging powerful tool for developmental biology and disease modeling (Dutta and Clevers, 2017; Hu et al., 2018).”
Advancements in organoid models emulating metastatic niches
Baumann, Z., Billy, É., & Scheidmann, M. C. (2026) · Trends in cancer · doi:10.1016/j.trecan.2026.02.005 · Cited by 5
Zhang, Y., Liu, K., He, H., Xiao, H., Fang, Z., Chen, X., & Li, H. (2024) · Environmental Science and Pollution Research · doi:10.1007/s11356-024-32256-7 · Cited by 6
“Hepatic parenchymal cells isolated from human fetus or adult liver also have the ability to form organoids, which can maintain the structure and function of the liver for a long time in vitro (Hu et al. 2018).”
Gastric Organoid, a Promising Modeling for Gastric Stem Cell Homeostasis and Therapeutic Application
Lee, S., Choi, J.-H., Park, S., & Kim, J. (2024) · International Journal of Stem Cells · doi:10.15283/ijsc23075 · Cited by 4
“3) (50, 51).”
Kanupriya, K., Verma, S., Sharma, V., Mishra, I., & Mishra, R. (2025) · Current Drug Research Reviews · doi:10.2174/0125899775369286250206050006 · Cited by 5
Zhang, K., Yuan, X., Lü, S., Shu, Y., Wang, C., Cen, J., Wu, B., & Hui, L. (2025) · Nature Protocols · doi:10.1038/s41596-025-01211-2 · Cited by 4
“Subsequently, Clevers and colleagues showed that FGF7, FGF10 and RSPO1-conditioned media were important for proliferation of human fetal hepatocytes 14 .”
Chen, Q., Li, C., Ding, W., & Kong, D. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202503273 · Cited by 5
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
Kim, H. M., Kim, Y., Kim, Y., Kim, Y. J., & Ko, K. S. (2023) · Preventive Nutrition and Food Science · doi:10.3746/pnf.2023.28.3.360 · Cited by 6
“Several studies have suggested that OrgPH morphology potentially exhibits a grape-like or hollow shape, whereas others have also suggested that it forms a rosette shape (Hu et al., 2018; Brooks et al., 2021; Nuciforo and Heim, 2020; Peng et al., 2021).”
BackgroundWu, H., Yang, A., Stelloo, S., Roos, F. J. M., Morsche, R. H. M. T., Verkerk, A. H., Velez, M. V. L., Wingens, L., de Wilt, J. H. W., Sauerwein, R. W., et al. (2025) · Disease Models & Mechanisms · doi:10.1242/dmm.050883 · Cited by 7
“However, the establishment and maintenance of these hepatocyte-derived organoids remain challenging (Hu et al., 2018; Peng et al., 2021).”
Raggi, C. C., Selleri, S., M’Callum, M.-A., & Paganelli, M. (2022) · Current Protocols · doi:10.1002/cpz1.389 · Cited by 4
Cellular therapies in liver and pancreatic diseases
Giuli, L., Santopaolo, F., Pallozzi, M., Pellegrino, A., Coppola, G., Gasbarrini, A., & Ponziani, F. R. (2022) · Digestive and Liver Disease · doi:10.1016/j.dld.2022.11.013 · Cited by 4
Tong, Y., Ueyama-Toba, Y., & Mizuguchi, H. (2023) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2023.101432 · Cited by 4
Kidney Organoid Derived from Human Pluripotent and Adult Stem Cells for Disease Modeling
Kang, H. M. (2023) · Development & Reproduction · doi:10.12717/dr.2023.27.2.57 · Cited by 4
“Since then, many other organoids, such as those of the liver, kidney, pancreas, stomach, uterus, prostate, and mammary gland, have been generated using stem cells from their own respective tissues (Barker et al., 2010; Karthaus et al., 2014; Boj et al., 2015; Hu et al., 2018; Sachs et al., 2018; Fitzgerald et al., 201…”
BackgroundLiu, Y., Tan, J., Zhang, N., Li, W., & Fu, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115671 · Cited by 5
“Notably, organoids from different hosts retained distinct initial sizes [42], resulting in the matching of strainers of different sizes.”
BackgroundOkumura, A., Aoshima, K., & Tanimizu, N. (2024) · Regenerative Therapy · doi:10.1016/j.reth.2024.05.020 · Cited by 6
Zeng, B., Xu, L., Wang, G., Shi, R., Wang, K., Wang, S., & Li, C. (2024) · The Ocular Surface · doi:10.1016/j.jtos.2024.08.014 · Cited by 4
Zhao, J. Z., Li, W., Guo, X., Wang, H., Rogers, J. A., & Huang, Y. Y. (2020) · MRS Bulletin · doi:10.1557/mrs.2020.253 · Cited by 13
Hao, X., & Li, W. (2021) · Oncology Letters · doi:10.3892/ol.2021.12494 · Cited by 4
Cell identity conversion in liver regeneration after injury
He, Q., Cui, L., Yuan, X., Wang, M., & Hui, L. (2022) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2022.101921 · Cited by 4
Valle-Encinas, E., Aleksieva, N., Martinez, C. V., Dawes, M., Zverev, M., Müller, M., Offergeld, A., Smalley, M. J., Hogan, C., Forbes, S. J., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.09.374462 · Cited by 4
Single organoid RNA-sequencing reveals high organoid-to-organoid variabilityPreprint
Gehling, K., Parekh, S., Schneider, F., Kirchner, M., Kondylis, V., Nikopoulou, C., & Tessarz, P. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.22.469588 · Cited by 4
“Hepatocyte-derived organoids, so called ‘Hep-Orgs’ consist mostly of progenitors and hepatocytes (Hu et al. 2018).”
BackgroundMarsee, A., Ritchie, A., Myszczyszyn, A., Ye, S., Chang, J., Ardisasmita, A. I., Joore, I. P., Castro-Alpízar, J., Fuchs, S. A., Schneeberger, K., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.10.598262 · Cited by 4
“Unlike previous studies, which report the absence of cholangiocyte markers in hepatocyte organoids 19,20,36 , hepatobiliary organoids in expansion conditions upregulate the expression of KRT7 and contain bi-phenotypic cells which co-express KRT19 and ALB.”
BackgroundMethodResultInfluentialDai, Q., Wang, J., Lin, Z., Yu, D., Yang, H., Zhang, J., Li, X., Zeng, J., Hu, H., Ni, C., et al. (2025) · Small Methods · doi:10.1002/smtd.202500425 · Cited by 3
Self-citation
Metadata
- Authors
- Hu, H., Gehart, H., Artegiani, B., LÖpez-Iglesias, C., Dekkers, F., Basak, O., van Es, J., Chuva de Sousa Lopes, S. M., Begthel, H., Korving, J., van den Born, M., Zou, C., Quirk, C., Chiriboga, L., Rice, C. M., Ma, S., Rios, A., Peters, P. J., de Jong, Y. P., & Clevers, H.
- Affiliations
- Royal Netherlands Academy of Arts and Sciences (NL)
- Weill Cornell Medicine (US)
- Rockefeller University (US)
- NYU Langone Health (US)
- University of Hong Kong (HK)
- Princess Máxima Center (NL)
- Maastricht University (NL)
- Corresponding author
- Clevers, Hans
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 175
- Issue
- 6
- Pages
- 1591-1606.e19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2903148550
- Cited by
- 837
- References
- 68
- Citations by year
- 2026: 74 · 2025: 114 · 2024: 141 · 2023: 122 · 2022: 118 · 2021: 134 · 2020: 95 · 2019: 38 · 2018: 1
- FWCI
- 41.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- MKMD (114021012)
- Netherlands Organization for Scientific Research (NWO-ZonMw
- Koerber Foundation
- National Natural Science Foundation of China (31501179)
- Foundation for Outstanding Young Scientist in Shandong Province (BS2014SW004)
- Future Scientist Program of Chinese Scholarship Council (CSC
- NWO-ZonMW (016.166.119)
- NWO/VENI (863.15.015)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- hepatocyte organoids, 3D organoid culture, primary hepatocytes, partial hepatectomy, hepatocyte proliferation, liver regeneration, cholangiocytes, engraftment, mouse hepatocytes, human hepatocytes
- MeSH terms
- Animals, Cells, Cultured, Humans, Mice, Inbred BALB C, Organoids, Stem Cells, Time Factors, Mice, Knockout, Cell Culture Techniques, Hepatocytes, Cell Proliferation, Mice
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
