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.
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?
The formation of organoids recapitulates a 3D in vivo-like microenvironment that may compensate for the lack of structural support for tissue formation in the damaged extracellular matrix environment when used as xenografts.
“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]
The Summary (p. 3) describes a 3D organoid culture that retains key hepatocyte features, and the engraftment results (p. 13) show that its cells repopulate damaged mouse livers. The paper does not say that organoids compensate for deficient structural support in damaged extracellular matrix. Indeed, the engraftment methods (pp. 12, 24) say the organoids were digested into single cells before transplantation, rather than used as intact 3D xenografts. (LLM, conf=0.89)
Experimental — accuracy not yet measuredHepatocyte-derived organoids undergo an initial 30-day quiescent phase post-transplantation, followed by rapid and extensive liver repopulation akin to that of primary hepatocytes.
“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]
The section “Human Hep-Orgs Engraft and Repopulate Damaged Mouse Liver” (p. 12) reports stable serum human albumin for the first 30 days in mice receiving fetal organoids, followed by graft proliferation at the same rate as primary-cell controls. It also reports an initial lag and subsequent proliferation for organoids derived from primary human hepatocytes (p. 13), but does not establish that their lag lasted 30 days or that either graft was strictly quiescent. (LLM, conf=0.85)
Experimental — accuracy not yet measuredMultiplexed CRISPR base-editing is versatile and flexible for cancer modeling across several epithelial tissues by mutating liver, endometrium, and organoids.
“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]
The Highlights (p. 2) identify this paper as a study of mouse and human hepatocyte organoids, supporting its citation for liver organoids. The paper does not report multiplexed CRISPR base-editing, endometrial organoids, or cancer modeling across several epithelial tissues; the citing authors describe that demonstration as their own. (LLM, conf=0.85)
Experimental — accuracy not yet measuredFunctional intestinal organoids have a relatively thick mucus layer because mature goblet cells secrete mucus.
“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]
The section on murine hepatocyte organoids (p. 5) describes liver-derived organoids, not mucus-producing intestinal organoids. Searches for goblet cells and mucus found no passage addressing the claimed thick mucus layer. Figure 2 (p. 7) uses PAS staining to assess glycogen in hepatocyte organoids, not intestinal mucus. (LLM, conf=0.76)
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.
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 · see citing works
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 · see citing works
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 · see citing works
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 · 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
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
CEL-seq2: sensitive highly-multiplexed single-cell RNA-Seq
Hashimshony, T., Senderovich, N., Avital, G., Klochendler, A., de Leeuw, Y., Anavy, L., Gennert, D., Li, S., Livak, K. J., Rozenblatt-Rosen, O., et al. (2016) · Genome Biology · doi:10.1186/s13059-016-0938-8 · Cited by 1,125 · see citing works
Somatic mutations of the β-catenin gene are frequent in mouse and human hepatocellular carcinomas
Coste, A. D. L., Romagnolo, B., Billuart, P., Renard, C.-A., Buendia, M., Soubrane, O., Fabrè, M., Chelly, J., Beldjord, C., Kahn, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.15.8847 · Cited by 1,121 · see citing works
Single-cell spatial reconstruction reveals global division of labour in the mammalian liver
Halpern, K. B., Shenhav, R., Matcovitch-Natan, O., Tóth, B., Lemze, D., Golan, M., Massasa, E. E., Baydatch, S., Landen, S., Moor, A. E., et al. (2017) · Nature · doi:10.1038/nature21065 · Cited by 1,059 · see citing works
Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors
Huang, P., He, Z., Ji, S., Sun, H., Xiang, D., Liu, C., Hu, Y., Wang, X., & Hui, L. (2011) · Nature · doi:10.1038/nature10116 · Cited by 864 · see citing works
Hippo Pathway Activity Influences Liver Cell Fate
Yimlamai, D., Christodoulou, C., Galli, G. G., Yanger, K., Pepe-Mooney, B., Gurung, B., Shrestha, K., Cahan, P., Stanger, B. Z., & Camargo, F. D. (2014) · Cell · doi:10.1016/j.cell.2014.03.060 · Cited by 857 · see citing works
Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors
Sekiya, S., & Suzuki, A. (2011) · Nature · doi:10.1038/nature10263 · Cited by 846 · 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
Self-citationFuruyama, K., Kawaguchi, Y., Akiyama, H., Horiguchi, M., Kodama, S., Kuhara, T., Hosokawa, S., Elbahrawy, A., Soeda, T., Koizumi, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.722 · Cited by 830 · see citing works
In Vitro Expansion of Human Gastric Epithelial Stem Cells and Their Responses to Bacterial Infection
Bartfeld, S., Bayram, T., van de Wetering, M., Huch, M., Begthel, H., Kujala, P., Vries, R., Peters, P. J., & Clevers, H. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.09.042 · Cited by 820 · see citing works
Self-citationLiver Regeneration after Partial Hepatectomy
Michalopoulos, G. K. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.090675 · Cited by 713 · see citing works
Organoid culture systems for prostate epithelial and cancer tissue
Drost, J., Karthaus, W. R., Gao, D., Driehuis, E., Sawyers, C. L., Chen, Y., & Clevers, H. C. (2016) · Nature Protocols · doi:10.1038/nprot.2016.006 · Cited by 694 · see citing works
Self-citationNault, J., Mallet, M., Pilati, C., Caldéraro, J., Bioulac‐Sage, P., Laurent, C., Laurent, A., Cherqui, D., Balabaud, C. P., & Zucman‐Rossi, J. (2013) · Nature Communications · doi:10.1038/ncomms3218 · Cited by 691 · see citing works
Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver
Wang, B., Zhao, L., Fish, M., Logan, C. Y., & Nusse, R. (2015) · Nature · doi:10.1038/nature14863 · Cited by 674 · see citing works
Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming
Miyajima, A., Tanaka, M., & Itoh, T. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.04.010 · Cited by 570 · see citing works
Direct Reprogramming of Human Fibroblasts to Functional and Expandable Hepatocytes
Huang, P., Zhang, L., Gao, Y., He, Z., Yao, D., Wu, Z., Cen, J., Chen, X., Liu, C., Hu, Y., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.01.003 · Cited by 560 · see citing works
Bipotential Adult Liver Progenitors Are Derived from Chronically Injured Mature Hepatocytes
Tarlow, B. D., Pelz, C., Naugler, W. E., Wakefield, L., Wilson, E. M., Finegold, M. J., & Grompe, M. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.09.008 · Cited by 533 · see citing works
Cholangiocytes 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
Cholangiocarcinomas can originate from hepatocytes in mice
Fan, B., Malato, Y., Calvisi, D. F., Naqvi, S., Razumilava, N., Ribback, S., Gores, G. J., Dombrowski, F., Evert, M., Chen, X., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63212 · Cited by 529 · see citing works
The ploidy conveyor of mature hepatocytes as a source of genetic variation
Duncan, A. W., Taylor, M. H., Hickey, R. D., Hanlon Newell, A. E., Lenzi, M. L., Olson, S. B., Finegold, M. J., & Grompe, M. (2010) · Nature · doi:10.1038/nature09414 · Cited by 525 · see citing works
Hybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer
Font-Burgada, J., Shalapour, S., Ramaswamy, S., Hsueh, B., Rossell, D., Umemura, A., Taniguchi, K., Nakagawa, H., Valasek, M. A., Ye, L., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.026 · Cited by 486 · see citing works
Robust cellular reprogramming occurs spontaneously during liver regeneration
Yanger, K., Zong, Y., Maggs, L. R., Shapira, S. N., Maddipati, R., Aiello, N. M., Thung, S. N., Wells, R. G., Greenbaum, L. E., & Stanger, B. Z. (2013) · Genes & Development · doi:10.1101/gad.207803.112 · Cited by 484 · see citing works
A precursor—product relationship exists between oval cells and hepatocytes in rat liver
Evarts, R. P., Nagy, P., Marsden, E. R., & Thorgeirsson, S. S. (1987) · Carcinogenesis · doi:10.1093/carcin/8.11.1737 · Cited by 447 · see citing works
van Amerongen, R., Bowman, A. N., & Nusse, R. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.05.023 · Cited by 446 · see citing works
Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration
Malato, Y., Naqvi, S., Schürmann, N., Ng, R., Wang, B., Zape, J., Kay, M. A., Grimm, D., & Willenbring, H. (2011) · Journal of Clinical Investigation · doi:10.1172/jci59261 · Cited by 434 · see citing works
Adult Hepatocytes Are Generated by Self-Duplication Rather than Stem Cell Differentiation
Yanger, K., Knigin, D., Zong, Y., Maggs, L., Gu, G., Akiyama, H., Pikarsky, E., & Stanger, B. Z. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.06.003 · Cited by 426 · see citing works
Genetic and Epigenetic Variations in iPSCs: Potential Causes and Implications for Application
Liang, G., & Zhang, Y. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.07.001 · Cited by 368 · see citing works
The RSPO–LGR4/5–ZNRF3/RNF43 module controls liver zonation and size
Planas-Paz, L., Orsini, V., Boulter, L., Calabrese, D., Pikiolek, M., Nigsch, F., Xie, Y., Roma, G., Donovan, A., Marti, P., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3337 · Cited by 359 · see citing works
Inflammatory Cytokine TNFα Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture
Peng, W. C., Logan, C. Y., Fish, M., Anbarchian, T., Aguisanda, F., Álvarez-Varela, A., Wu, P., Jin, Y., Zhu, J., Li, B., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.012 · Cited by 331 · see citing works
Isolation and Culture of Adult Mouse Hepatocytes
Li, W., Ralphs, K. L., & Tosh, D. (2010) · Methods in molecular biology · doi:10.1007/978-1-59745-019-5_13 · Cited by 303 · see citing works
Functional and genetic deconstruction of the cellular origin in liver cancer
Marquardt, J. U., Andersen, J. B., & Thorgeirsson, S. S. (2015) · Nature reviews. Cancer · doi:10.1038/nrc4017 · Cited by 300 · see citing works
Mouse liver repopulation with hepatocytes generated from human fibroblasts
Zhu, S.-Y., Rezvani, M., Harbell, J., Mattis, A. N., Wolfe, A., Benet, L., Willenbring, H., & Ding, S. (2014) · Nature · doi:10.1038/nature13020 · Cited by 266 · see citing works
Katsuda, T., Kawamata, M., Hagiwara, K., Takahashi, R.-U., Yamamoto, Y., Camargo, F. D., & Ochiya, T. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.10.007 · Cited by 260 · see citing works
Schaub, J. R., Malato, Y., Gormond, C., & Willenbring, H. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.003 · Cited by 254 · cited 1× · see citing works
“Indeed, several recent lineage tracing approaches failed to find support for a stem cell with cholangiocyte characteristics (Schaub et al., 2014; Yanger et al., 2014).”
Cellular Homeostasis and Repair in the Mammalian Liver
Stanger, B. Z. (2015) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170255 · Cited by 248 · see citing works
Genetic and epigenetic stability of human pluripotent stem cells
Lund, R., Närvä, E., & Lahesmaa, R. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3271 · Cited by 243 · see citing works
Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury
Lin, S., Nascimento, E. M., Gajera, C. R., Chen, L., Neuhöfer, P., Garbuzov, A., Wang, S., & Artandi, S. E. (2018) · Nature · doi:10.1038/s41586-018-0004-7 · Cited by 241 · see citing works
Oncostatin M and hepatocyte growth factor induce hepatic maturation via distinct signaling pathways
Kamiya, A., Kinoshita, T., & Miyajima, A. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02140-8 · Cited by 213 · see citing works
Efficient temporally controlled targeted somatic mutagenesis in hepatocytes of the mouse
Schuler, M. J., Dierich, A., Chambon, P., & METZGER, D. (2004) · genesis · doi:10.1002/gene.20039 · Cited by 175 · see citing works
Partial Hepatectomy in the Mouse: Technique and Perioperative Management
Greene, A. K., & Puder, M. (2003) · Journal of Investigative Surgery · doi:10.1080/08941930390194424 · Cited by 168 · see citing works
Liver Zonation Occurs Through a β-Catenin–Dependent, c-Myc–Independent Mechanism
Burke, Z. D., Reed, K. R., Phesse, T. J., Sansom, O. J., Clarke, A. R., & Tosh, D. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.02.063 · Cited by 163 · see citing works
Sell, S., Nichols, M., Becker, F. F., & Leffert, H. L. (1974) · PubMed · Cited by 157 · see citing works
Long-term culture and expansion of primary human hepatocytes
Levy, G., Bomze, D., Heinz, S., Ramachandran, S. D., Noerenberg, A., Cohen, M., Shibolet, O., Sklan, E., Braspenning, J., & Nahmias, Y. (2015) · Nature Biotechnology · doi:10.1038/nbt.3377 · Cited by 155 · see citing works
EpCAM and the biology of hepatic stem/progenitor cells
Dollé, L., Theise, N. D., Schmelzer, E., Boulter, L., Gires, O., & van Grunsven, L. A. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00069.2014 · Cited by 129 · see citing works
Sekiya, S., & Suzuki, A. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.01.005 · Cited by 125 · see citing works
Tanimizu, N., Nishikawa, Y., Ichinohe, N., Akiyama, H., & Mitaka, T. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.517243 · Cited by 105 · see citing works
Regeneration of mouse liver after partial hepatectomy.
Yokoyama, H. O., Wilson, M. E., TSUBOI, K. K., & Stowell, R. E. (1953) · PubMed · Cited by 89 · see citing works
Billerbeck, E., Mommersteeg, M. C., Shlomai, A., Xiao, J. W., Andrus, L., Bhatta, A., Vercauteren, K., Michailidis, E., Dorner, M., Krishnan, A., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.04.022 · Cited by 87 · see citing works
Self-citationLiver Stem Cells, Where Art Thou?
Grompe, M. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.08.004 · Cited by 81 · see citing works
Sustained telomere length in hepatocytes and cholangiocytes with increasing age in normal liver
Verma, S., Tachtatzis, P., Penrhyn-Lowe, S., Scarpini, C. G., Jurk, D., von Zglinicki, T., Coleman, N., & Alexander, G. (2012) · Hepatology · doi:10.1002/hep.25787 · Cited by 73 · see citing works
Hepatoblast-Like Progenitor Cells Derived From Embryonic Stem Cells Can Repopulate Livers of Mice
Li, F., Liu, P., Liu, C., Xiang, D., Deng, L., Li, W., Wangensteen, K. J., Jianguo, S., Ma, Y., Hui, L., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.08.042 · Cited by 72 · see citing works
Adult Mouse Liver Contains Two Distinct Populations of Cholangiocytes
Li, B., Dorrell, C., Canaday, P. S., Pelz, C., Haft, A., Finegold, M. J., & Grompe, M. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.06.003 · Cited by 66 · see citing works
Fah Knockout Animals as Models for Therapeutic Liver Repopulation
Grompe, M. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-55780-9_20 · Cited by 42 · see citing works
Engelhardt, N. V., Lazareva, M. N., Abelev, G. I., Uryvaeva, I. V., Factor, V. M., & Brodsky, V. Y. (1976) · Nature · doi:10.1038/263146a0 · Cited by 40 · see citing works
Liu, Y., Cao, L., Chen, R., Zhou, X., Fan, X., Liang, Y., Jia, R., Wang, H., Liu, G., Guo, Y., et al. (2015) · Stem Cells · doi:10.1002/stem.2072 · Cited by 26 · see citing works
Sox9 marks adult organ progenitors
Huch, M., & Clevers, H. C. (2010) · Nature Genetics · doi:10.1038/ng0111-9 · Cited by 25 · see citing works
Self-citationAccelerated telomere reduction and hepatocyte senescence in tolerated human liver allografts
Aini, W., Miyagawa‐Hayashino, A., Ozeki, M., Salah, A., Hirata, M., Tamaki, K., Üemoto, S., & Haga, H. (2014) · Transplant Immunology · doi:10.1016/j.trim.2014.06.008 · Cited by 19 · see citing works
Swenson, S. E. (2011) · Hepatology · doi:10.1002/hep.24717 · Cited by 12 · see citing works
Flagged first, then by citations
1 of the 68 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Human organoids: model systems for human biology and medicine
Kim, J., Koo, B.-K., & Knoblich, J. A. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0259-3 · Cited by 2,187 · see citing works
Ginès, P., Krag, A., Abraldes, J. G., Solà, E., Fabrellas, N., & Kamath, P. S. (2021) · The Lancet · doi:10.1016/s0140-6736(21)01374-x · Cited by 1,663 · see citing works
Hofer, M., & Lutolf, M. P. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00279-y · Cited by 1,184 · see citing works
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
Corrò, C., Novellasdemunt, L., & Li, V. S. W. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00120.2020 · Cited by 561 · see citing works
High-resolution 3D imaging of fixed and cleared organoids
Dekkers, J. F., Alieva, M., Wellens, L. M., Ariese, H. C., Jamieson, P. R., Vonk, A. M., Amatngalim, G. D., Hu, H., Oost, K. C., Snippert, H. J. G., et al. (2019) · Nature Protocols · doi:10.1038/s41596-019-0160-8 · Cited by 534 · see citing works
Self-citationHuman Organoids: Tools for Understanding Biology and Treating Diseases
Schutgens, F., & Clevers, H. C. (2019) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012419-032611 · Cited by 506 · see citing works
Self-citationGiobbe, G. G., Crowley, C., Luni, C., Campinoti, S., Khedr, M., Kretzschmar, K., De Santis, M. M., Zambaiti, E., Michielin, F., Meran, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13605-4 · Cited by 500 · see citing works
Self-citationHuman organoids in basic research and clinical applications
Tang, X.-Y., Wu, S., Wang, D., Chu, C., Hong, Y., Tao, M., Hu, H., Xu, M., Guo, X. L., & Liu, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01024-9 · Cited by 509 · see citing works
Self-citationKatsura, H., Sontake, V., Tata, A., Kobayashi, Y., Edwards, C. E., Heaton, B. E., Konkimalla, A., Asakura, T., Mikami, Y., Fritch, E. J., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.10.005 · Cited by 416 · see citing works
Disease modelling in human organoids
Lancaster, M. A., & Huch, M. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.039347 · Cited by 379 · see citing works
High-Fidelity Drug-Induced Liver Injury Screen Using Human Pluripotent Stem Cell–Derived Organoids
Shinozawa, T., Kimura, M., Cai, Y., Saiki, N., Yoneyama, Y., Ouchi, R., Koike, H., Maezawa, M., Zhang, R.-R., Dunn, A., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.002 · Cited by 378 · see citing works
Organoids in immunological research
Bar-Ephraim, Y. E., Kretzschmar, K., & Clevers, H. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0248-y · Cited by 361 · see citing works
Self-citationLiver organoids: from basic research to therapeutic applications
Prior, N., Inacio, P., & Huch, M. (2019) · Gut · doi:10.1136/gutjnl-2019-319256 · Cited by 356 · see citing works
Inflammatory Cytokine TNFα Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture
Peng, W. C., Logan, C. Y., Fish, M., Anbarchian, T., Aguisanda, F., Álvarez-Varela, A., Wu, P., Jin, Y., Zhu, J., Li, B., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.012 · Cited by 331 · see citing works
Polystyrene microplastics induce hepatotoxicity and disrupt lipid metabolism in the liver organoids
Cheng, W., Li, X., Zhou, Y., Yu, H., Xie, Y., Guo, H., Wang, H., Li, Y., Feng, Y., & Wang, Y. (2021) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2021.150328 · Cited by 317 · see citing works
Building 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-citationArtegiani, B., Hendriks, D. F. G., Beumer, J., Kok, R. N. U., Zheng, X., Joore, I. P., Lopes, S. M. C. D. S., van Zon, J. S., Tans, S. J., & Clevers, H. C. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0472-5 · Cited by 302 · see citing works
Self-citationModeling neoplastic disease with spheroids and organoids
Zanoni, M., Cortesi, M., Zamagni, A., Arienti, C., Pignatta, S., & Tesei, A. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00931-0 · Cited by 265 · see citing works
Weaver, R. J., Blomme, E. A. G., Chadwick, A. E., Copple, I. M., Gerets, H. H. J., Goldring, C. E., Guillouzo, A., Hewitt, P. G., Ingelman‐Sundberg, M., Jensen, K. G., et al. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0048-x · Cited by 254 · see citing works
Microtechnology-based methods for organoid models
Velasco, V., Shariati, S. A., & Esfandyarpour, R. (2020) · Microsystems & Nanoengineering · doi:10.1038/s41378-020-00185-3 · Cited by 253 · see citing works
Hendriks, D. F. G., Brouwers, J. F. H. M., Hamer, K. M., Geurts, M. H., Luciana, L., Massalini, S., López‐Iglesias, C., Peters, P. J., Colman, M. J. R., Lopes, S. M. C. D. S., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01680-4 · Cited by 251 · see citing works
Self-citationThree-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models
Urzì, O., Gasparro, R., Costanzo, E., Luca, A. D., Giavaresi, G., Fontana, S., & Alessandro, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512046 · Cited by 247 · see citing works
Mechano-modulatory synthetic niches for liver organoid derivation
Sorrentino, G., Rezakhani, S., Yildiz, E., Nuciforo, S., Heim, M. H., Lutolf, M. P., & Schoonjans, K. (2020) · Nature Communications · doi:10.1038/s41467-020-17161-0 · Cited by 224 · see citing works
Bioengineering Approaches for the Advanced Organoid Research
Yi, S. A., Zhang, Y., Rathnam, C., Pongkulapa, T., & Lee, K. (2021) · Advanced Materials · doi:10.1002/adma.202007949 · Cited by 218 · 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
Wang, S., Wang, X., Tan, Z., Su, Y., Liu, J., Chang, M., Yan, F., Chen, J., Chen, T., Li, C., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0242-8 · Cited by 211 · see citing works
Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer
Lõhmussaar, K., Oka, R., Espejo Valle-Inclan, J., Smits, M. H. H., Wardak, H., Korving, J., Begthel, H., Proost, N., van de Ven, M., Kranenburg, O. W., et al. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.03.012 · Cited by 211 · see citing works
Self-citationThree-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure
Yang, H., Sun, L., Pang, Y., Hu, D., Xu, H., Mao, S., Peng, W., Wang, Y., Xu, Y., Zheng, Y., et al. (2020) · Gut · doi:10.1136/gutjnl-2019-319960 · Cited by 205 · see citing works
An Automated Organoid Platform with Inter-organoid Homogeneity and Inter-patient Heterogeneity
Jiang, S., Zhao, H., Zhang, W., Wang, J., Liu, Y., Cao, Y., Zheng, H., Hu, Z., Wang, S., Zhu, Y., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100161 · Cited by 188 · see citing works
Self-citationCRISPR-Cas Tools and Their Application in Genetic Engineering of Human Stem Cells and Organoids
Hendriks, D. F. G., Clevers, H. C., & Artegiani, B. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.10.014 · Cited by 196 · see citing works
Self-citationGalan, E. A., Zhao, H., Wang, X., Dai, Q., Huck, W. T. S., & Ma, S. (2020) · Matter · doi:10.1016/j.matt.2020.08.034 · Cited by 192 · see citing works
Self-citationWang, J., Wu, Y. Q., Li, G., Zhou, F., Wu, X., Wang, M., Liu, X., Tang, H., Bai, L., Geng, Z., et al. (2024) · Advanced Materials · doi:10.1002/adma.202309875 · Cited by 190 · see citing works
Applications of organoids for cancer biology and precision medicine
Lo, Y.-H., Karlsson, K., & Kuo, C. J. (2020) · Nature Cancer · doi:10.1038/s43018-020-0102-y · Cited by 182 · see citing works
The landscape of gene mutations in cirrhosis and hepatocellular carcinoma
Müller, M., Bird, T. G., & Nault, J. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.01.019 · Cited by 178 · see citing works
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.2023.03.006 · Cited by 184 · see citing works
Defining Adult Stem Cell Function at Its Simplest: The Ability to Replace Lost Cells through Mitosis
Post, Y., & Clevers, H. C. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.07.002 · Cited by 176 · see citing works
Self-citationA Chemically Defined Hydrogel for Human Liver Organoid Culture
Ye, S., Boeter, J. W. B., Mihajlovic, M., van Steenbeek, F. G., van Wolferen, M. E., Oosterhoff, L. A., Marsee, A., Caiazzo, M., van der Laan, L. J. W., Penning, L. C., et al. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202000893 · Cited by 165 · see citing works
Somatic cell-derived organoids as prototypes of human epithelial tissues and diseases
Fujii, M., & Sato, T. (2020) · Nature Materials · doi:10.1038/s41563-020-0754-0 · Cited by 165 · see citing works
Organoids to model liver disease
Nuciforo, S., & Heim, M. H. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2020.100198 · Cited by 164 · see citing works
Patient-derived organoids in precision cancer medicine
Tong, L., Cui, W., Zhang, B., Fonseca, P., Zhao, Q. C., Zhang, P., Xu, B., Zhang, Q., Li, Z., Seashore-Ludlow, B. A., et al. (2024) · Med · doi:10.1016/j.medj.2024.08.010 · Cited by 173 · see citing works
Hendriks, D. F. G., Artegiani, B., Hu, H., Lopes, S. M. C. D. S., & Clevers, H. C. (2020) · Nature Protocols · doi:10.1038/s41596-020-00411-2 · Cited by 159 · see citing works
Self-citationOrganoid cultures for cancer modeling
Yan, H. H. N., Chan, A., Lai, F. P.-L., & Leung, S. Y. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.05.012 · Cited by 163 · see citing works
Next-Generation Surrogate Wnts Support Organoid Growth and Deconvolute Frizzled Pleiotropy In Vivo
Miao, Y., Ha, A., de Lau, W., Yuki, K., Santos, A. J. M., You, C., Geurts, M. H., Puschhof, J., Pleguezuelos-Manzano, C., Peng, W. C., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.07.020 · Cited by 151 · see citing works
Self-citationSun, L., Wang, Y., Cen, J., Ma, X., Cui, L., Qiu, Z., Zhang, Z., Li, H., Yang, R., Wang, C., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0359-5 · Cited by 160 · see citing works
Cell therapy for advanced liver diseases: repair or rebuild
Dwyer, B. J., Macmillan, M. T., Brennan, P. N., & Forbes, S. J. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2020.09.014 · Cited by 141 · see citing works
Single-cell atlas of human liver development reveals pathways directing hepatic cell fates
Wesley, B. T., Ross, A. D. B., Muraro, D., Miao, Z., Saxton, S., Tomaz, R. A., Morell, C. M., Ridley, K., Zacharis, E. D., Petrus-Reurer, S., et al. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00989-7 · Cited by 146 · see citing works
Organoids 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
3D Cell Cultures: Evolution of an Ancient Tool for New Applications
Cacciamali, A., Villa, R., & Dotti, S. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.836480 · Cited by 144 · see citing works
Cell Plasticity in Liver Regeneration
Li, W., Li, L., & Hui, L. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.01.007 · Cited by 167 · see citing works
Large‐Scale Production of LGR5‐Positive Bipotential Human Liver Stem Cells
Schneeberger, K., Sánchez‐Romero, N., Ye, S., van Steenbeek, F. G., Oosterhoff, L. A., Pla Palacin, I., Chen, C., van Wolferen, M. E., van Tienderen, G., Lieshout, R., et al. (2020) · Hepatology · doi:10.1002/hep.31037 · Cited by 141 · see citing works
Self-citationOrganoid based personalized medicine: from bench to bedside
Li, Y., Tang, P., Cai, S., Peng, J., & Hua, G. (2020) · Cell Regeneration · doi:10.1186/s13619-020-00059-z · Cited by 138 · see citing works
Evaluating CRISPR-based prime editing for cancer modeling and CFTR repair in organoids
Geurts, M. H., de Poel, E., Pleguezuelos-Manzano, C., Oka, R., Carrillo, L., Andersson-Rolf, A., Boretto, M., Brunsveld, J. E., van Boxtel, R., Beekman, J. M., et al. (2021) · Life Science Alliance · doi:10.26508/lsa.202000940 · Cited by 151 · see citing works
Self-citationLiver Organoids: Recent Developments, Limitations and Potential
Harrison, S. P., Baumgarten, S., Verma, R., Lunov, O., Dejneka, A., & Sullivan, G. J. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.574047 · Cited by 141 · see citing works
Decarli, M. C., do Amaral, R. L. F., dos Santos, D. P., Tofani, L. B., Katayama, E. T., Rezende, R. A., da Silva, J. V. L., Swiech, K., Suazo, C. A. T., Mota, C., et al. (2021) · Biofabrication · doi:10.1088/1758-5090/abe6f2 · Cited by 132 · see citing works
Exploring the human lacrimal gland using organoids and single-cell sequencing
Bannier-Hélaouët, M., Post, Y., Korving, J., Bustos, M. T., Gehart, H., Begthel, H., Bar‐Ephraïm, Y. E., van der Vaart, J., Kalmann, R., Imhoff, S. M., et al. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.02.024 · Cited by 130 · see citing works
Self-citationGame changers in science and technology - now and beyond
Betz, U. A. K., Arora, L., Assal, R. A., de Azevedo, H. F. Z., Baldwin, J., Becker, M. S., Bostock, S., Cheng, V. W. T., Egle, T., Ferrari, N., et al. (2023) · Technological Forecasting and Social Change · doi:10.1016/j.techfore.2023.122588 · Cited by 146 · see citing works
Yap-Sox9 signaling determines hepatocyte plasticity and lineage-specific hepatocarcinogenesis
Liu, Y., Zhuo, S., Zhou, Y., Ma, L., Sun, Z., Wu, X., Wang, X. W., Gao, B., & Yang, Y. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.11.010 · Cited by 129 · see citing works
The Influence of Sex Hormones in Liver Function and Disease
Kasarinaite, A., Sinton, M. C., Saunders, P. T. K., & Hay, D. C. (2023) · Cells · doi:10.3390/cells12121604 · Cited by 134 · see citing works
Developments and Opportunities for 3D Bioprinted Organoids
Ya, R., Yang, X., Ma, Z., Sun, X., Zhang, Y., Li, W., Yang, H. S., Qiang, L., Yang, Z., Liu, Y., et al. (2021) · International Journal of Bioprinting · doi:10.18063/ijb.v7i3.364 · Cited by 129 · see citing works
Research Progress, Challenges, and Breakthroughs of Organoids as Disease Models
Huang, Y., Huang, Z., Tang, Z., Chen, Y., Huang, M., Liu, H., Huang, W., Ye, Q., & Jia, B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.740574 · Cited by 128 · see citing works
Lõhmussaar, K., Kopper, O., Korving, J., Begthel, H., Vreuls, C. P. H., van Es, J. H., & Clevers, H. C. (2020) · Nature Communications · doi:10.1038/s41467-020-16432-0 · Cited by 122 · see citing works
Self-citationHydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures
Urciuolo, A., Giobbe, G. G., Dong, Y., Michielin, F., Brandolino, L., Magnussen, M., Gagliano, O., Selmin, G., Scattolini, V., Raffa, P., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37953-4 · Cited by 121 · see citing works
Self-citationCancer research using organoid technology
Kretzschmar, K. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-020-01990-z · Cited by 120 · see citing works
In vitro grafting of hepatic spheroids and organoids on a microfluidic vascular bed
Bonanini, F., Kurek, D., Previdi, S., Nicolas, A., Hendriks, D., de Ruiter, S., Meyer, M., Clapés Cabrer, M., Dinkelberg, R., García, S. B., et al. (2022) · Angiogenesis · doi:10.1007/s10456-022-09842-9 · Cited by 112 · see citing works
Self-citation3D and organoid culture in research: physiology, hereditary genetic diseases and cancer
Suarez-Martinez, E., Suazo-Sanchez, I., Celis-Romero, M., & Carnero, A. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00775-w · Cited by 118 · see citing works
Diba, M., Spaans, S., Hendrikse, S. I. S., Bastings, M. M. C., Schotman, M. J. G., van Sprang, J. F., Wu, D. J., Hoeben, F. J. M., Janssen, H. M., & Dankers, P. Y. W. (2021) · Advanced Materials · doi:10.1002/adma.202008111 · Cited by 111 · see citing works
Hydrogels for Liver Tissue Engineering
Ye, S., Boeter, J. W. B., Penning, L. C., Spee, B., & Schneeberger, K. (2019) · Bioengineering · doi:10.3390/bioengineering6030059 · Cited by 112 · see citing works
Seidlitz, T., Koo, B., & Stange, D. E. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00662-2 · Cited by 108 · see citing works
Liver organoid as a 3D in vitro model for drug validation and toxicity assessment
Brooks, A., Liang, X., Zhang, Y., Zhao, C., Roberts, M. S., Wang, H., Zhang, L., & Crawford, D. H. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105608 · Cited by 109 · see citing works
Human fetal brain self-organizes into long-term expanding organoids
Hendriks, D. F. G., Pagliaro, A., Andreatta, F., Ma, Z., van Giessen, J., Massalini, S., López‐Iglesias, C., van Son, G. J. F., DeMartino, J., Damen, M. J. A., et al. (2024) · Cell · doi:10.1016/j.cell.2023.12.012 · Cited by 106 · see citing works
Self-citationCRISPR engineering in organoids for gene repair and disease modelling
Geurts, M. H., & Clevers, H. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-022-00013-5 · Cited by 103 · see citing works
Self-citationExtracellular matrix requirements for gastrointestinal organoid cultures
Rezakhani, S., Gjorevski, N., & Lutolf, M. P. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.121020 · Cited by 100 · see citing works
Antigen retrieval and clearing for whole-organ immunofluorescence by FLASH
Messal, H. A., Almagro, J., Thin, M. Z., Tedeschi, A., Ciccarelli, A., Blackie, L., Anderson, K. I., Miguel‐Aliaga, I., van Rheenen, J., & Behrens, A. (2020) · Nature Protocols · doi:10.1038/s41596-020-00414-z · Cited by 97 · see citing works
Machine perfusion of the liver and bioengineering
Schlegel, A. A., Mergental, H., Fondevila, C., Porte, R. J., Friend, P. J., & Dutkowski, P. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.02.009 · Cited by 99 · see citing works
Airway organoids as models of human disease
van der Vaart, J., & Clevers, H. C. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13075 · Cited by 97 · see citing works
Self-citationBiologically inspired approaches to enhance human organoid complexity
Holloway, E. M., Capeling, M. M., & Spence, J. R. (2019) · Development · doi:10.1242/dev.166173 · Cited by 96 · see citing works
Torresi, J., Tran, B. M., Christiansen, D., Earnest-Silveira, L., Schwab, R., & Vincan, E. (2019) · BMC Cancer · doi:10.1186/s12885-019-5916-6 · Cited by 97 · see citing works
Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research
Düzağaç, F., Saorin, G., Memeo, L., Canzonieri, V., & Rizzolio, F. (2021) · Cancers · doi:10.3390/cancers13040737 · Cited by 94 · see citing works
Olgasi, C., Cucci, A., & Follenzi, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176215 · Cited by 100 · see citing works
Modelling metabolic diseases and drug response using stem cells and organoids
Hu, W., & Lazar, M. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00733-z · Cited by 98 · see citing works
Katsuda, T., Matsuzaki, J., Yamaguchi, T., Yamada, Y., Prieto‐Vila, M., Hosaka, K., Takeuchi, A., Saito, Y., & Ochiya, T. (2019) · eLife · doi:10.7554/elife.47313 · Cited by 95 · see citing works
Guo, J., Duan, L., He, X., Li, S., Wu, Y., Xiang, G., Bao, F., Yang, L., Shi, H., Gao, M., et al. (2021) · Advanced Science · doi:10.1002/advs.202004680 · Cited by 94 · see citing works
Self-citationZhang, L., Ma, X.-J.-N., Fei, Y.-Y., Han, H., Xu, J., Cheng, L., & Li, X. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108004 · Cited by 93 · see citing works
Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives
Wang, J., Sun, S., & Deng, H. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.08.001 · Cited by 91 · see citing works
Genetics of Hepatocellular Carcinoma: Approaches to Explore Molecular Diversity
Caruso, S., O’Brien, D. R., Cleary, S. P., Roberts, L. R., & Zucman‐Rossi, J. (2020) · Hepatology · doi:10.1002/hep.31394 · Cited by 94 · see citing works
Hallmarks of stemness in mammalian tissues
Beumer, J., & Clevers, H. C. (2024) · Cell stem cell · doi:10.1016/j.stem.2023.12.006 · Cited by 91 · see citing works
Self-citationVerstegen, 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
Self-citationTanimizu, N., Ichinohe, N., Sasaki, Y., Itoh, T., Sudo, R., Yamaguchi, T., Katsuda, T., Ninomiya, T., Tokino, T., Ochiya, T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23575-1 · Cited by 93 · see citing works
Liu, G., Wei, J., Li, X., Tian, M., Wang, Z., Shen, C., Sun, W. F., Li, C., Li, X., Lv, E., et al. (2022) · Advanced Science · doi:10.1002/advs.202202505 · Cited by 87 · see citing works
McCarron, S., Bathon, B., Conlon, D. M., Abbey, D., Rader, D. J., Gawronski, K., Brown, C. D., Olthoff, K. M., Shaked, A., & Raabe, T. D. (2021) · Hepatology · doi:10.1002/hep.31857 · Cited by 89 · see citing works
Iordachescu, A., Hughes, E. A. B., Joseph, S., Hill, E. J., Grover, L. M., & Metcalfe, A. D. (2021) · npj Microgravity · doi:10.1038/s41526-021-00146-8 · Cited by 87 · see citing works
SARS-CoV-2 infection and replication in human gastric organoids
Giobbe, G. G., Bonfante, F., Jones, B. C., Gagliano, O., Luni, C., Zambaiti, E., Perin, S., Laterza, C., Busslinger, G. A., Stuart, H. T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26762-2 · Cited by 86 · see citing works
Self-citationComplex in vitro model: A transformative model in drug development and precision medicine
Wang, L., Hu, D., Xu, J., Hu, J., & Wang, Y. (2023) · Clinical and Translational Science · doi:10.1111/cts.13695 · Cited by 87 · see citing works
Intestinal organ chips for disease modelling and personalized medicine
Özkan, A., LoGrande, N., Feitor, J. F., Goyal, G., & Ingber, D. E. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00968-3 · Cited by 89 · see citing works
Generation of human adult hepatocyte organoids with metabolic functions
Igarashi, R., Oda, M., Okada, R., Yano, T., Takahashi, S., Pastuhov, S., Matano, M., Masuda, N., Togasaki, K., Ohta, Y., et al. (2025) · Nature · doi:10.1038/s41586-025-08861-y · Cited by 85 · see citing works
Towards a better understanding of diabetes mellitus using organoid models
Beydag-Tasöz, B. S., Yennek, S., & Grapin‐Botton, A. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00797-x · Cited by 83 · see citing works
Kim, S.-H., & Chang, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512528 · Cited by 89 · see citing works
Tissue clearing to examine tumour complexity in three dimensions
Almagro, J., Messal, H. A., Thin, M. Z., van Rheenen, J., & Behrens, A. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00382-w · Cited by 81 · see citing works
Kim, H., Im, I., Jeon, J. S., Kang, E.-H., Lee, H., Jo, S., Kim, J., Woo, D., Choi, Y. J., Kim, H. J., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121575 · Cited by 84 · see citing works
- 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
