Evidence map›Paper›PMID 25533785›Full record

ArticleCell2015

Long-term culture of genome-stable bipotent stem cells from adult human liver.

Meritxell Huch, Helmuth Gehart, Ruben van Boxtel, Karien Hamer, Francis Blokzijl, Monique M A Verstegen, Ewa Ellis, Martien van Wenum, Sabine A Fuchs, Joep de Ligt and 13 more

Registry-linked trialAbstract read
In one paragraph

Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04342286 (To Establish a Reproducible Organoid Culture Model With Human Kidney Cancer), which is not on this map. Cited by 881 papers.

0numbers the graph read from it
0cells of the map it votes in
881citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04342286 completednot on this mapstarted 2020, after this paper: background citation

To Establish a Reproducible Organoid Culture Model With Human Kidney Cancer

TypeobservationalSponsorChinese University of Hong KongRan2020 to 2021Enrolled20ConditionsKidney CancerArmsOrganoid culture
3 · Its place in the literature

Who cites it

881 citing papers in PubMed.

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  8. The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026
    Review
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  12. Urinary Volatile Organic Compound Metabolites Are Associated With MASLD/MASH in Humans and Induce Steatosis in Liver Organoids.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
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821 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Meritxell HuchHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands. Electronic address: m.huch@gurdon.cam.ac.uk.
Helmuth GehartHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Ruben van BoxtelHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Karien HamerHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Francis BlokzijlHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Monique M A VerstegenDepartment of Surgery, Erasmus MC-University Medical Center, Postbus 2040, 3000 CA Rotterdam, the Netherlands.
Ewa EllisUnit for Transplantation Surgery, Department of CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, Hälsovägen, Flemingsberg, SE-141 86 Stockholm, Sweden.
Martien van WenumSurgical Laboratory, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Sabine A FuchsDivision of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands.
Joep de LigtHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Marc van de WeteringHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Hubrecht Organoid Technology (HUB), Uppsalalaan 8, 3584CT, Utrecht, the Netherlands.
Nobuo SasakiHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Susanne J BoersDivision of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands.
Hans KempermanDepartment of Clinical Chemistry and Haematology, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands.
Jeroen de JongeDepartment of Surgery, Erasmus MC-University Medical Center, Postbus 2040, 3000 CA Rotterdam, the Netherlands.
Jan N M IjzermansDepartment of Surgery, Erasmus MC-University Medical Center, Postbus 2040, 3000 CA Rotterdam, the Netherlands.
Edward E S NieuwenhuisDivision of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands.
Ruurdtje HoekstraSurgical Laboratory, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Stephen StromDivision of Pathology, Department of Laboratory Medicine, Karolinska Institute, Alfred Nobels Alle 8, F 56 141-86 Stockholm, Sweden.
Robert R G VriesHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Hubrecht Organoid Technology (HUB), Uppsalalaan 8, 3584CT, Utrecht, the Netherlands.
Luc J W van der LaanDepartment of Surgery, Erasmus MC-University Medical Center, Postbus 2040, 3000 CA Rotterdam, the Netherlands.
Edwin CuppenHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Hans CleversHubrecht Institute-KNAW, University Medical Centre Utrecht, CancerGenomics.nl, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands. Electronic address: h.clevers@hubrecht.eu.

Funding

Wellcome Trust 092096Wellcome Trust 104151
6 · The paper itself

Abstract

Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy.

Indexed as

Organ Culture TechniquesAnimalsGenomic InstabilityHepatocytesHumansLiverMiceOrganoids

Identifiers

PMID25533785
PMCPMC4313365

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.