Evidence map›Paper›PMID 39495812›Full record

ArticlePloS one2024

Overcoming problematic growth phenotypes in organoids from patients with monogenic GI disease.

Katlynn Bugda Gwilt, Jay R Thiagarajah

Abstract read
In one paragraph

Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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

  1. Pooled it
  2. Article
  3. Review
  4. 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

2 authors.

Katlynn Bugda GwiltDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.ORCID 0000-0001-9616-6934
Jay R ThiagarajahDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.ORCID 0000-0002-1437-325X

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
COngenital Diarrhea and Enteropathy (PediCODE) Consortium and BioRepositoryRC2DK118640 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI James Richard Goldenring, Izumi Kaji · 2019 to 2026
$14.8M
Identifying Immune and Epithelial Network Signatures in Very Early Onset Inflammatory Bowel DiseaseRC2DK122532 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI KLEIN, CHRISTOPH, MUISE, ALEIXO M · 2020 to 2024
$9.1M
The role of TTC7A in apical lumen formation and polarized trafficking in the intestinal epitheliumF32DK130267 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI BUGDA GWILT, KATLYNN · 2022 to 2025
$248k
NIDDK NIH HHS F32 DK130267NIDDK NIH HHS P30 DK034854NIDDK NIH HHS RC2 DK118640NIDDK NIH HHS RC2 DK122532
6 · The paper itself

Abstract

Patient-derived organoids provide a unique model system to explore disease-causing mutations ex vivo. By using organoids from duodenal or colonic biopsies of pediatric patients with intestinal epithelial disorders, we can directly assay the patient cells to tailor treatment to their unique disease state. The advent of organoid technology from patients with severe intestinal disorders such as Congenital Diarrhea Enteropathies (CoDE) and Very-Early-Onset Inflammatory Bowel Disease (VEO-IBD) has allowed for rapid advances in the understanding of and the treatment of these monogenic disorders. Still, the expansion of these lines for scalable studies is not trivial, and success rates of expansion are variable between groups, and even lab members within the same group. These protocols have been validated on patients with CoDE or VEO-IBD and age-matched control patients. Here, we present our recommended protocols for the cultivation of organoids from pediatric patients with CoDE and VEO-IBD. These protocols have been validated on organoids generated from the duodenum (duodenoids), ileum (ileoids), colon (colonoids) and iPSC-derived intestinal colonoids from pediatric healthy donors or donors with CoDE or VEO-IBD (Gwilt et al., 2023). Using our modified culture media, extended culture times from biopsy preparation and thawing frozen lines, gentle passaging techniques with the incomplete removal of the organoids from the matrigel, and modified monolayer protocols (Maeda et al., 2023; Maeda et al., 2022), we have been able to successfully culture and expand several lines for more than 5 years. The conditions and protocols used here provide a basis for reproducible phenotypes, scaling for larger functional studies on patient lines, and for reproducibility of results between several investigators. We provide a useful starting point and troubleshooting guidelines for the optimization of culturing organoids from any patient with novel disease pathology.

Indexed as

OrganoidsPhenotypeBiopsyCell Culture TechniquesChildCollagenColonDrug CombinationsDuodenumGastrointestinal DiseasesHumansInduced Pluripotent Stem CellsInflammatory Bowel DiseasesLamininProteoglycansCollagenDrug CombinationsLamininmatrigelProteoglycans

Identifiers

PMID39495812
PMCPMC11534248

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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.