Evidence map›Paper›PMID 25828392›Full record

ArticleExperimental and molecular pathology2015

Intestinal organoids: a model of intestinal fibrosis for evaluating anti-fibrotic drugs.

Eva S Rodansky, Laura A Johnson, Sha Huang, Jason R Spence, Peter D R Higgins

Abstract read
In one paragraph

Article in Experimental and molecular pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
–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.

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

53 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. AnBiofabrication · 2025
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Characterization of patient-derived intestinal organoids for modelling fibrosis in Inflammatory Bowel Disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
    Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Anti-fibrotics in inflammatory bowel diseases: Challenges and successes.Advances in pharmacology (San Diego, Calif.) · 2024
    Review
  18. Article
  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

5 authors.

Eva S RodanskyDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Laura A JohnsonDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Sha HuangDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Jason R SpenceDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Peter D R HigginsDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. Electronic address: phiggins@med.umich.edu.

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
Mechanisms of intestine developmentK01DK091415 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SPENCE, JASON · 2011 to 2015
$700k
Mechanisms and Prevention of TGF-beta-induced Intestinal FibrosisK08DK080172 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HIGGINS, PETER D.R. · 2008 to 2010
$461k
NIDDK NIH HHS 5P30DK034933NIDDK NIH HHS K01 DK091415NIDDK NIH HHS K01DK091415NIDDK NIH HHS K08 DK080172NIDDK NIH HHS P30 DK034933
6 · The paper itself

Abstract

BACKGROUND &

aimsIntestinal fibrosis is a critical complication of Crohn's disease (CD). Current in vitro models of intestinal fibrosis cannot model the complex intestinal architecture, while in vivo rodent models do not fully recapitulate human disease and have limited utility for large-scale screening. Here, we exploit recent advances in stem cell derived human intestinal organoids (HIOs) as a new human model of fibrosis in CD.

methodsHuman pluripotent stem cells were differentiated into HIOs. We identified myofibroblasts, the key effector cells of fibrosis, by immunofluorescence staining for alpha-smooth muscle actin (αSMA), vimentin, and desmin. We examined the fibrogenic response of HIOs by treatment with transforming growth factor beta (TGFβ) in the presence or absence of the anti-fibrotic drug spironolactone. Fibrotic response was assayed by expression of fibrogenic genes (COL1A1 (collagen, type I, alpha 1), ACTA2 (alpha smooth muscle actin), FN1 (fibronectin 1), MYLK (myosin light chain kinase), and MKL1 (megakaryoblastic leukemia (translocation) 1)) and proteins (αSMA).

resultsImmunofluorescent staining of organoids identified a population of myofibroblasts within the HIO mesenchyme. TGFβ stimulation of HIOs produced a dose-dependent pro-fibrotic response. Spironolactone treatment blocked the fibrogenic response of HIOs to TGFβ.

conclusionsHIOs contain myofibroblasts and respond to a pro-fibrotic stimulus in a manner that is consistent with isolated human myofibroblasts. HIOs are a promising model system that might bridge the gap between current in vitro and in vivo models of intestinal fibrosis in IBD.

Indexed as

ActinsCalcium-Binding ProteinsCell DifferentiationCells, CulturedCollagen Type ICollagen Type I, alpha 1 ChainEmbryonic Stem CellsFibronectinsFibrosisHumansIntestinesMyofibroblastsMyosin-Light-Chain KinaseOrganoidsPluripotent Stem CellsSpironolactoneACTA2 protein, humanActinsCalcium-Binding ProteinsCollagen Type ICollagen Type I, alpha 1 ChainFibronectinsFN1 protein, humanMRTFA protein, humanMYLK protein, humanMyosin-Light-Chain KinaseSpironolactoneTrans-ActivatorsTransforming Growth Factor betaDrug screeningFibrosis modelMyofibroblastsOrganoidTGFβ

Identifiers

PMID25828392
PMCPMC5915372

What OpenQuestion holds

Textmetadata
LicenceTDM
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.