Evidence map›Paper›PMID 34918082›Full record

ArticleInflammatory bowel diseases2022

Development of a Personalized Intestinal Fibrosis Model Using Human Intestinal Organoids Derived From Induced Pluripotent Stem Cells.

Hannah Q Estrada, Shachi Patel, Shervin Rabizadeh, David Casero, Stephan R Targan, Robert J Barrett

Abstract read
In one paragraph

Article in Inflammatory bowel diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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.

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

15 citing papers in PubMed.

  1. Article
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  14. Intersection of stem cell biology and engineering towards next generationFrontiers in bioengineering and biotechnology · 2022
    Review
  15. Intestinal strictures in Crohn's disease: a 2021 update.Therapeutic advances in gastroenterology · 2022
    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

6 authors.

Hannah Q EstradaBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Shachi PatelBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Shervin RabizadehDivision of Pediatric Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USAand.
David CaseroF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Stephan R TarganF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Robert J BarrettBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0001-5966-0706

Funding

Using polygenic scores to enhance both variant discovery, and understanding of functional consequences of genetic variation in IBD.P01DK046763 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI MCGOVERN, DERMOT PATRICK · 1992 to 2020
$31.1M
Utilizing the Phenomics of IBD to Enhance Gene DiscoveryU01DK062413 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI Dermot Patrick McGovern · 2002 to 2026
$12.2M
NIDDK NIH HHS P01 DK046763NIDDK NIH HHS U01 DK062413
6 · The paper itself

Abstract

backgroundIntestinal fibrosis is a serious complication of Crohn's disease. Numerous cell types including intestinal epithelial and mesenchymal cells are implicated in this process, yet studies are hampered by the lack of personalized in vitro models. Human intestinal organoids (HIOs) derived from induced pluripotent stem cells (iPSCs) contain these cell types, and our goal was to determine the feasibility of utilizing these to develop a personalized intestinal fibrosis model.

methodsiPSCs from 2 control individuals and 2 very early onset inflammatory bowel disease patients with stricturing complications were obtained and directed to form HIOs. Purified populations of epithelial and mesenchymal cells were derived from HIOs, and both types were treated with the profibrogenic cytokine transforming growth factor β (TGFβ). Quantitative polymerase chain reaction and RNA sequencing analysis were used to assay their responses.

resultsIn iPSC-derived mesenchymal cells, there was a significant increase in the expression of profibrotic genes (Col1a1, Col5a1, and TIMP1) in response to TGFβ. RNA sequencing analysis identified further profibrotic genes and demonstrated differential responses to this cytokine in each of the 4 lines. Increases in profibrotic gene expression (Col1a1, FN, TIMP1) along with genes associated with epithelial-mesenchymal transition (vimentin and N-cadherin) were observed in TGFβ -treated epithelial cells.

conclusionsWe demonstrate the feasibility of utilizing iPSC-HIO technology to model intestinal fibrotic responses in vitro. This now permits the generation of near unlimited quantities of patient-specific cells that could be used to reveal cell- and environmental-specific mechanisms underpinning intestinal fibrosis.

Indexed as

Induced Pluripotent Stem CellsOrganoidsFibrosisHumansIntestinesTransforming Growth Factor betaTransforming Growth Factor betadisease modelinghuman intestinal organoidsinduced pluripotent stem cellsintestinal fibrosis

Identifiers

PMID34918082
PMCPMC9074870

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Registered trials

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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.