Evidence map›Paper›PMID 26993089›Full record

ArticleEMBO reports2016

R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders.

Natalia Lugli, Irene Kamileri, Adrian Keogh, Thomas Malinka, Michalis E Sarris, Iannis Talianidis, Olivier Schaad, Daniel Candinas, Deborah Stroka, Thanos D Halazonetis

Open access · bronzeAbstract read
In one paragraph

Article in EMBO reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

39 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Review
  3. Gallbladder cholangiocyte organoids.Biology of the cell · 2025
    Review
  4. Review
  5. Organoids in biliary atresia.World journal of pediatric surgery · 2025
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. A gene edited pig model for studying LGR5Frontiers in genome editing · 2024
    Review
  11. The utilisation of biliary organoids for biomedical applications.Frontiers in bioengineering and biotechnology · 2024
    Review
  12. Liver organoid culture methods.Cell & bioscience · 2023
    Review
  13. Review
  14. Application and Progress of Cultured Models of Gallbladder Carcinoma.Journal of clinical and translational hepatology · 2023
    Review
  15. Article
  16. Review
  17. Article
  18. Primary human organoids models: Current progress and key milestones.Frontiers in bioengineering and biotechnology · 2023
    Review
  19. Review
  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 2 countries.

Natalia LugliDepartment of Molecular Biology, University of Geneva, Geneva, Switzerland National Centre of Competence in Research "Frontiers in Genetics", Geneva, Switzerland.
Irene KamileriDepartment of Molecular Biology, University of Geneva, Geneva, Switzerland.
Adrian KeoghDepartment of Clinical Research, Clinic of Visceral Surgery and Medicine, University of Bern, Bern, Switzerland.
Thomas MalinkaDepartment of Clinical Research, Clinic of Visceral Surgery and Medicine, University of Bern, Bern, Switzerland.
Michalis E SarrisBiomedical Sciences Research Center Alexander Fleming, Vari, Greece.
Iannis TalianidisBiomedical Sciences Research Center Alexander Fleming, Vari, Greece.
Olivier SchaadDepartment of Biochemistry, University of Geneva, Geneva, Switzerland.
Daniel CandinasDepartment of Clinical Research, Clinic of Visceral Surgery and Medicine, University of Bern, Bern, Switzerland.
Deborah StrokaDepartment of Clinical Research, Clinic of Visceral Surgery and Medicine, University of Bern, Bern, Switzerland deborah.stroka@dkf.unibe.ch thanos.halazonetis@unige.ch.
Thanos D HalazonetisDepartment of Molecular Biology, University of Geneva, Geneva, Switzerland deborah.stroka@dkf.unibe.ch thanos.halazonetis@unige.ch.
University of Bern · CHUniversity of Geneva · CHAlexander Fleming Biomedical Sciences Research Center · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pioneering studies within the last few years have allowed the in vitro expansion of tissue-specific adult stem cells from a variety of endoderm-derived organs, including the stomach, small intestine, and colon. Expansion of these cells requires activation of the receptor Lgr5 by its ligand R-spondin 1 and is likely facilitated by the fact that in healthy adults the stem cells in these organs are highly proliferative. In many other adult organs, such as the liver, proliferating cells are normally not abundant in adulthood. However, upon injury, the liver has a strong regenerative potential that is accompanied by the emergence of Lgr5-positive stem cells; these cells can be isolated and expanded in vitro as organoids. In an effort to isolate stem cells from non-regenerating mouse livers, we discovered that healthy gallbladders are a rich source of stem/progenitor cells that can be propagated in culture as organoids for more than a year. Growth of these organoids was stimulated by R-spondin 1 and noggin, whereas in the absence of these growth factors, the organoids differentiated partially toward the hepatocyte fate. When transplanted under the liver capsule, gallbladder-derived organoids maintained their architecture for 2 weeks. Furthermore, single cells prepared from dissociated organoids and injected into the mesenteric vein populated the liver parenchyma of carbon tetrachloride-treated mice. Human gallbladders were also a source of organoid-forming stem cells. Thus, under specific growth conditions, stem cells can be isolated from healthy gallbladders, expanded almost indefinitely in vitro, and induced to differentiate toward the hepatocyte lineage.

Indexed as

AnimalsBiomarkersCarrier ProteinsCell DifferentiationCells, CulturedGallbladderGene Expression ProfilingHumansLiverMiceMice, TransgenicNoggin ProteinOrganoidsProtein Kinase InhibitorsReceptors, Transforming Growth Factor betaStem CellsBiomarkersCarrier ProteinsNoggin ProteinProtein Kinase InhibitorsReceptors, Transforming Growth Factor betaRSPO1 protein, mouseThrombospondinsgallbladdernogginorganoidsR‐spondin 1stem cells

Identifiers

PMID26993089
PMCPMC5341509
OpenAlexW2299725955

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.