Evidence map›Paper›PMID 26915950›Full record

ArticleScientific reports2016

Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure.

Ewart W Kuijk, Shauna Rasmussen, Francis Blokzijl, Meritxell Huch, Helmuth Gehart, Pim Toonen, Harry Begthel, Hans Clevers, Aron M Geurts, Edwin Cuppen

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 4% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Research Progress on Hepatitis E Virus Culture.Pathogens (Basel, Switzerland) · 2025
    Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Cell-Based Regeneration and Treatment of Liver Diseases.International journal of molecular sciences · 2021
    Review
  12. Review
  13. Article
  14. Creating rat hepatocyte organoid as anWorld journal of stem cells · 2020
    Article
  15. Review
  16. Review
  17. Article
  18. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Ewart W KuijkHubrecht Institute, KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
Shauna RasmussenDepartment of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Francis BlokzijlHubrecht Institute, KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
Meritxell HuchWellcome Trust/MRC Stem Cell Institute, Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Rd, Cambridge CB2 1QN, UK.
Helmuth GehartHubrecht Institute, KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
Pim ToonenHubrecht Institute, KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
Harry BegthelHubrecht Institute, KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
Hans CleversHubrecht Institute, KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
Aron M GeurtsDepartment of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Edwin CuppenHubrecht Institute, KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
University Medical Center Utrecht · NLMedical College of Wisconsin · USWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

INTEGRATED PHYSIOLOGY TRAINING--MOLECULE TO ORGANISMT32HL007852 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI Matthew Robert Hodges · 1996 to 2026
$6.5M
Advanced genetic engineering technology developmentDP2OD008396 · OD · MEDICAL COLLEGE OF WISCONSIN · PI GEURTS, ARON M · 2011 to 2011
$2.3M
NHLBI NIH HHS T32 HL007852NIH HHS DP2 OD008396Wellcome Trust 104151/Z/14/Z
6 · The paper itself

Abstract

The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah(-/-) Il2rg(-/-) rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat.

Indexed as

Stem Cell TransplantationAnimalsBiomarkersCarrier ProteinsCell Culture TechniquesCell DifferentiationCell ProliferationCells, CulturedHepatocytesHydrolasesInterleukin Receptor Common gamma SubunitLiverLiver FailureLiver RegenerationLiver TransplantationNoggin ProteinBiomarkersCarrier ProteinsfumarylacetoacetaseHydrolasesInterleukin Receptor Common gamma SubunitNoggin ProteinWnt3A Protein

Identifiers

PMID26915950
PMCPMC4768167
OpenAlexW2281468449

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.