The DOI matches its Crossref record; 76 of the 78 references it cites were found in a registry or an index.
Liver Stem Cells: Experimental Findings and Implications for Human Liver Disease
Open accessAbstract
Evidence from human histopathology and experimental studies with rodents and zebrafish has shown that hepatocytes and cholangiocytes may function as facultative stem cells for each other in conditions of impaired regeneration. The interpretation of the findings derived from these studies has generated considerable discussion and some controversies. This review examines the evidence obtained from the different experimental models and considers implications that these studies may have for human liver disease.
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
“Notably, in chronic liver diseases, HHs with expression of progenitor-associated markers were also documented in regenerative nodules (Michalopoulos and Khan, 2015; Yoon et al., 2011”
From In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity (2018) · cites this paper as Michalopoulos and Khan, 2015
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
“Cell plasticity has lately been recognized to play an important role in liver regeneration (Kopp et al., 2016; Li et al., 2016; Michalopoulos and Khan, 2015”
From In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity (2018) · cites this paper as Michalopoulos and Khan, 2015
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
Michalopoulos, G. K., & DeFrances, M. C. (1997) · Science · doi:10.1126/science.276.5309.60 · Cited by 2,828
Self-citationLong-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
Mederacke, I., Hsu, C. C., Troeger, J. S., Huebener, P., Mu, X., Dapito, D. H., Pradere, J.-P., & Schwabe, R. F. (2013) · Nature Communications · doi:10.1038/ncomms3823 · Cited by 1,443
Michalopoulos, G. K. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21172 · Cited by 1,384
Self-citationHippo 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
Furuyama, K., Kawaguchi, Y., Akiyama, H., Horiguchi, M., Kodama, S., Kuhara, T., Hosokawa, S., Elbahrawy, A., Soeda, T., Koizumi, M., et al. (2010) · Nature Genetics · doi:10.1038/ng.722 · Cited by 841
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
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
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
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
Hepatic progenitor cells of biliary origin with liver repopulation capacity
Lu, W.-Y., Bird, T. G., Boulter, L., Tsuchiya, A., Cole, A. M., Hay, T., Guest, R. V., Wojtacha, D., Man, T. Y., Mackinnon, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3203 · Cited by 479
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
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
TWEAK induces liver progenitor cell proliferation
Jakubowski, A., Ambrose, C., Parr, M., Lincecum, J. M., Wang, M. Z., Zheng, T. S., Browning, B., Michaelson, J. S., Baestcher, M., Wang, B., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23486 · Cited by 419
The origin and liver repopulating capacity of murine oval cells
Wang, X., Foster, M., Al-Dhalimy, M., Lagasse, E., Finegold, M., & Grompe, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1734199100 · Cited by 410
Liver Progenitor Cells Yield Functional Hepatocytes in Response to Chronic Liver Injury in Mice
Español–Suñer, R., Carpentier, R., Van Hul, N., Legry, V., Achouri, Y., Cordi, S., Jacquemin, P., Lemaigre, F., & Leclercq, I. A. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.08.024 · Cited by 356
Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes
Sekiya, S., & Suzuki, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63065 · Cited by 348
In vivo differentiation of rat liver oval cells into hepatocytes.
Evarts, R. P., Nagy, P., Nakatsukasa, H., Marsden, E. R., & Thorgeirsson, S. S. (1989) · PubMed · Cited by 321
Michalopoulos, G. K., Barua, L., & Bowen, W. C. (2005) · Hepatology · doi:10.1002/hep.20600 · Cited by 319
Self-citationFujio, K., Evarts, R. P., Hu, Z., Marsden, E. R., & Thorgeirsson, S. S. (1994) · PubMed · Cited by 286
Principles of Liver Regeneration and Growth Homeostasis
Michalopoulos, G. K. (2012) · Comprehensive physiology · doi:10.1002/cphy.c120014 · Cited by 278
Self-citationCarpentier, R., Español‐Suñer, R., Hul, N. V., Kopp, J. L., Beaudry, J., Cordi, S., Antoniou, A., Raynaud, P., Lepreux, S., Jacquemin, P., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.06.049 · Cited by 271
Schaub, J. R., Malato, Y., Gormond, C., & Willenbring, H. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.003 · Cited by 254
He, J., Lu, H., Zou, Q., & Luo, L. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.11.045 · Cited by 247
Fetal phenotypic expression by adult rat hepatocytes on collagen gel/nylon meshes.
Sirica, A. E., Richards, W., Tsukada, Y., Sattler, C. A., & Pitot, H. C. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.1.283 · Cited by 246
Choi, T., Ninov, N., Stainier, D. Y. R., & Shin, D. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.10.019 · Cited by 244
Prospective isolation of a bipotential clonogenic liver progenitor cell in adult micePreprint
Dorrell, C., Erker, L. R., Schug, J., Kopp, J. L., Canaday, P. S., Fox, A. J., Smirnova, O., Duncan, A. W., Finegold, M. J., Sander, M., et al. (2011) · Genes & Development · doi:10.1101/gad.2029411 · Cited by 239
Expression of hepatic transcription factors during liver development and oval cell differentiation.
Nagy, P., Bisgaard, H. C., & Thorgeirsson, S. S. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.126.1.223 · Cited by 230
Clonal Tracing of Sox9+ Liver Progenitors in Mouse Oval Cell Injury
Tarlow, B., Finegold, M. J., & Grompe, M. (2014) · Hepatology · doi:10.1002/hep.27084 · Cited by 224
Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly
Alison, M. R., Islam, S., & Lim, S. G. (2008) · The Journal of Pathology · doi:10.1002/path.2453 · Cited by 213
Petersen, B. E., Zajac, V. F., & Michalopoulos, G. K. (1998) · Hepatology · doi:10.1002/hep.510270419 · Cited by 203
Self-citationExpression of Notch-1 and its ligand Jagged-1 in rat liver during liver regeneration
Köhler, C. N., Bell, A. W., Bowen, W. C., Monga, S. P., Fleig, W. E., & Michalopoulos, G. K. (2004) · Hepatology · doi:10.1002/hep.20156 · Cited by 195
Self-citationThe biliary epithelium gives rise to liver progenitor cells
Rodrigo-Torres, D., Affò, S., Coll, M., Morales-Ibanez, O., Millán, C., Blaya, D., Alvarez-Guaita, A., Rentero, C., José Lozano, J., Maestro, M. A., et al. (2014) · Hepatology · doi:10.1002/hep.27078 · Cited by 189
Ductular Reaction in the Livers
Desmet, V. J., Roskams, T., & Eyken, P. V. (1995) · Pathology - Research and Practice · doi:10.1016/s0344-0338(11)80870-8 · Cited by 189
Hepatic stellate cells contribute to progenitor cells and liver regeneration
Kordes, C., Sawitza, I., Götze, S., Herebıan, D., & Häussinger, D. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74119 · Cited by 177
Oval cell differentiation into hepatocytes in the acetylaminofluorene-treated regenerating rat liver
Golding, M., Sarraf, C., Lalani, E., Anilkumar, T. V., Edwards, R. J., Nagy, P., Thorgemsson, S. S., & Alison, M. R. (1995) · Hepatology · doi:10.1016/0270-9139(95)90635-5 · Cited by 154
Bralet, M., Branchereau, S., Bréchot, C., & Ferry, N. (1994) · PubMed Central · Cited by 150
Lineage fate of ductular reactions in liver injury and carcinogenesis
Jörs, S., Jeliazkova, P., Ringelhan, M., Thalhammer, J., Dürl, S., Ferrer, J., Sander, M., Heikenwalder, M., Schmid, R. M., Siveke, J. T., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78585 · Cited by 149
Tatematsu, M., Ho, R., Kaku, T., Ekem, J. K., & Farber, E. (1984) · PubMed Central · Cited by 144
Advances in liver regeneration
Michalopoulos, G. K. (2014) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2014.934358 · Cited by 138
Self-citationDemetris, A. J., Seaberg, E. C., Wennerberg, A. E. K., Ionellie, J., & Michalopoulos, G. K. (1996) · PubMed Central · Cited by 128
Self-citationThe antigen for Hep Par 1 antibody is the urea cycle enzyme carbamoyl phosphate synthetase 1
Butler, S. L., Dong, H., Cardona, D. M., Jia, M., Zheng, R., Zhu, H., Crawford, J. M., & Liu, C. (2007) · Laboratory Investigation · doi:10.1038/labinvest.3700699 · Cited by 128
Cell proliferation and renewal of normal hepatocytes and bile duct cells in adult mouse liver
Magami, Y., Azuma, T., Inokuchi, H., Kokuno, S., Moriyasu, F., Kawai, K., & Hattori, T. (2002) · Liver International · doi:10.1034/j.1600-0676.2002.01702.x · Cited by 124
Evarts, R. P., Hu, Z., Fujio, K., Marsden, E. R., & Thorgeirsson, S. S. (1993) · PubMed · Cited by 121
Limaye, P. B., Bowen, W. C., Orr, A. V., Luo, J., Tseng, G. C., & Michalopoulos, G. K. (2008) · Hepatology · doi:10.1002/hep.22221 · Cited by 120
Self-citationAlison, M. R., Golding, M., Lalani, E., Nagy, P., Thorgeirsson, S. S., & Sarraf, C. (1997) · Journal of Hepatology · doi:10.1016/s0168-8278(97)80051-7 · Cited by 119
Paku, S., Nagy, P., Kopper, L., & Thorgeirsson, S. S. (2004) · Hepatology · doi:10.1002/hep.20178 · Cited by 117
Induction and origin of hepatocytes in rat pancreas.
Reddy, J. K., Rao, M. S. R., Qureshi, S. A., Reddy, M. K., Scarpelli, D. G., & Lalwani, N. D. (1984) · The Journal of Cell Biology · doi:10.1083/jcb.98.6.2082 · Cited by 116
DeBaun, J. R., Rowley, J., Miller, E. C., & MILLER, J. A. (1968) · Experimental Biology and Medicine · doi:10.3181/00379727-129-33301 · Cited by 114
Stueck, A., & Wanless, I. R. (2015) · Hepatology · doi:10.1002/hep.27706 · Cited by 109
Rao, M. S. R., Dwivedi, R. S., Subborao, V., Usman, M. I., Scarpelli, D. G., Nemali, M. R., Yeldandi, A. V., Thangada, S., Kumar, S., & Reddy, J. K. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)80814-3 · Cited by 104
Gracz, A. D., Fuller, M. K., Wang, F., Li, L., Stelzner, M. G., Dunn, J., Martı́n, M. G., & Magness, S. T. (2013) · Stem Cells · doi:10.1002/stem.1391 · Cited by 101
Limaye, P. B., Alarcón, G., Walls, A. L., Nalesnik, M. A., Michalopoulos, G. K., Demetris, A. J., & Ochoa, E. R. (2008) · Laboratory Investigation · doi:10.1038/labinvest.2008.56 · Cited by 94
Self-citationEvarts, R. P., Nagy, P., Marsden, E. R., & Thorgeirsson, S. S. (1987) · PubMed · Cited by 93
Bile ductular damage induced by methylene dianiline inhibits oval cell activation.
Petersen, B. E., Zajac, V. F., & Michalopoulos, G. K. (1997) · PubMed · Cited by 89
Self-citationElmore, L. W., & Sirica, A. E. (1991) · PubMed · Cited by 88
Hepatocytes undergo phenotypic transformation to biliary epithelium in organoid cultures
Michalopoulos, G. K., Bowen, W. C., Mulé, K., López-Talavera, J. C., & Mars, W. M. (2002) · Hepatology · doi:10.1053/jhep.2002.34858 · Cited by 82
Self-citationBisgaard, H. C., Nagy, P., Santoni‐Rugiu, E., & Thorgeirsson, S. S. (1996) · Hepatology · doi:10.1002/hep.510230110 · Cited by 73
Exocrine Pancreatic Tissue in Human Liver
Wolf, H. K., Burchette, J. L., Garcia, J. A., & Michalopoulos, G. (1990) · The American Journal of Surgical Pathology · doi:10.1097/00000478-199006000-00011 · Cited by 67
Self-citationWeng, H., Cai, X., Yuan, X., Liebe, R., Dooley, S., Li, H., & Wang, T. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00178 · Cited by 52
Isse, K., Lesniak, A. J., Grama, K., Maier, J., Specht, S. M., Castillo‐Rama, M., Lunz, J. G., Roysam, B., Michalopoulos, G. K., & Demetris, A. J. (2012) · Hepatology · doi:10.1002/hep.26131 · Cited by 50
Self-citationExpression of hepatocyte growth factor mRNA during oval cell activation in the rat liver
Alison, M. R., Poulsom, R., Jeffery, R. E., Anilkumar, T. V., Jagoe, R., & Sarraf, C. (1993) · The Journal of Pathology · doi:10.1002/path.1711710410 · Cited by 50
Transdifferentiation of ductular cells into hepatocytes in regenerating hamster pancreas.
Makino, T., Usuda, N., Rao, S., Jk, R., & Dg, S. (1990) · PubMed · Cited by 48
Determining the fate of hepatic cells by lineage tracing: Facts and pitfalls
Lemaigre, F. P. (2014) · Hepatology · doi:10.1002/hep.27659 · Cited by 43
Gebhardt, R., Cruise, J. L., Houck, K. A., Luetteke, N., Novotny, A., Thaler, F., & Michalopoulos, G. K. (1986) · Differentiation · doi:10.1111/j.1432-0436.1986.tb00409.x · Cited by 39
Self-citationHu, Z., Evarts, R. P., Fujio, K., Marsden, E. R., & Thorgeirsson, S. S. (1995) · PubMed · Cited by 39
Elmore, L. W., & Sirica, A. E. (1992) · Hepatology · doi:10.1002/hep.1840160519 · Cited by 37
Trautwein, C., Will, M., Kubicka, S., Rakemann, T., Flemming, P., & Manns, M. P. (1999) · Oncogene · doi:10.1038/sj.onc.1203045 · Cited by 37
Guest, I., Ilic, Z., & Sell, S. (2010) · Hepatology · doi:10.1002/hep.23880 · Cited by 22
Magnus, I. A., Roe, D. A., & Bhutani, L. K. (1969) · Journal of Investigative Dermatology · doi:10.1038/jid.1969.167 · Cited by 22
Volk, A., Michalopoulos, G. K., Weidner, M., & Gebhardt, R. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.1227 · Cited by 21
Self-citationWhitehouse, T., & Wendon, J. A. (2013) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2013.08.010 · Cited by 17
eWeng, H., eCai, X., eYuan, X., eLiebe, R., eDooley, S., eLi, H., & eWang, T.-L. (2015) · Frontiers in Physiology · Cited by 11
Biliary Cells to the Rescue of Prometheus
Verfaillie, C. M. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.01.039 · Cited by 6
Streaming liver VII: DNA turnover in acinus zone‐3
Zajicek, G., & Schwartz‐Arad, D. (1990) · Liver International · doi:10.1111/j.1600-0676.1990.tb00448.x · Cited by 6
Lamers, W. H. (1990) · Hepatology · doi:10.1002/hep.1840120231 · Cited by 4
Cited by
Sorted by citations
Liver regeneration: biological and pathological mechanisms and implications
Michalopoulos, G. K., & Bhushan, B. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0342-4 · Cited by 998
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
Banales, J. M., Huebert, R. C., Karlsen, T., Strazzabosco, M., LaRusso, N. F., & Gores, G. J. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0125-y · Cited by 517
Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology
Russell, J. O., & Monga, S. P. (2018) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-044010 · Cited by 471
Hepatostat: Liver regeneration and normal liver tissue maintenance
Michalopoulos, G. K. (2017) · Hepatology · doi:10.1002/hep.28988 · Cited by 444
Self-citation
Metadata
- Authors
- Michalopoulos, G. K., & Khan, Z.
- Affiliations
- University of Pittsburgh (US)
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 149
- Issue
- 4
- Pages
- 876-882
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC4584191
- OpenAlex
- W2112926558
- Cited by
- 109
- References
- 78
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 13 · 2022: 10 · 2021: 11 · 2020: 11 · 2019: 10 · 2018: 18 · 2017: 8 · 2016: 10 · 2015: 3
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (2r01ca103958-06a1)
- National Cancer Institute (R01CA035373, R01-CA103958)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK096990)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD071834, K12HD052892)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- liver stem cells, cholangiocytes, hepatocytes, liver regeneration, liver disease, zebrafish model, rodent models
- MeSH terms
- Animals, Bile Ducts, Intrahepatic, Cell Differentiation, Gene Expression Regulation, Humans, Liver, Liver Diseases, Liver Regeneration, Stem Cells, Signal Transduction, Cell Lineage, Hepatocytes, Cell Proliferation
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
