Evidence map›Paper›PMID 25326803›Full record

ArticleNature medicine2014

An in vivo model of human small intestine using pluripotent stem cells.

Carey L Watson, Maxime M Mahe, Jorge Múnera, Jonathan C Howell, Nambirajan Sundaram, Holly M Poling, Jamie I Schweitzer, Jefferson E Vallance, Christopher N Mayhew, Ying Sun and 6 more

Abstract read
In one paragraph

Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 324 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
324citing papers in PubMed, 2 pooled it
46.3field-weighted citation impact, top 1% 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

324 citing papers in PubMed, 2 syntheses or guidelines pooled it, 571 citations in OpenAlex.

  1. Guiding Principles: Reporting Elements for Gastrointestinal Organoid Research.Cellular and molecular gastroenterology and hepatology · 2026
    Guideline
  2. Pooled it
  3. Regional organization of nutrient absorption across the small intestine.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  4. Article
  5. Review
  6. Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  7. Article
  8. Recent advancements and limitations of intestinal organoids for clinical applications.Progress in biomedical engineering (Bristol, England) · 2026
    Review
  9. Review
  10. Review
  11. Non-invasiveSurgery open science · 2026
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

264 more citing papers are in PubMed but not listed here.

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

16 authors at 3 institutions in 1 country.

Carey L Watson1] Department of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. [2] Department of General Surgery, University of Cincinnati, Cincinnati, Ohio, USA.
Maxime M MaheDepartment of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Jorge MúneraDepartment of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Jonathan C HowellDepartment of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Nambirajan SundaramDepartment of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Holly M PolingDepartment of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Jamie I SchweitzerDepartment of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Jefferson E VallanceDepartment of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Christopher N MayhewDepartment of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Ying SunDepartment of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Gregory Grabowski1] Department of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. [2] Synageva Corporation, Lexington, Massachusetts, USA.
Stacy R FinkbeinerDepartment of Internal Medicine, University of Michigan, Biomedical Science Research Building, Ann Arbor, Michigan, USA.
Jason R SpenceDepartment of Internal Medicine, University of Michigan, Biomedical Science Research Building, Ann Arbor, Michigan, USA.
Noah F Shroyer1] Department of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. [2] Department of Medicine, Section of Gastroenterology &Hepatology, Baylor College of Medicine, Houston, Texas, USA.
James M WellsDepartment of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Michael A Helmrath1] Department of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. [2] Department of General Surgery, University of Cincinnati, Cincinnati, Ohio, USA.
Cincinnati Children's Hospital Medical Center · USUniversity of Michigan–Ann Arbor · USUniversity of Cincinnati · US

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OMARY, BISHR · 1986 to 2021
$22.5M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR026314 · NCRR · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E. · 2009 to 2011
$14.3M
Intestinal Stem Cell Consortium Coordinating CenterU01DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2009 to 2018
$6.5M
STUDIES OF GAUCHER DISEASE: A PROTOTYPE LIPIDOSISR01DK036729 · NIDDK · MOUNT SINAI SCHOOL OF MEDICINE OF CUNY · PI GRABOWSKI, GREGORY A. · 1986 to 2011
$4.5M
Investigation of Regional Identity in Human Intestinal Stem CellsU01DK103117 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI HELMRATH, MICHAEL A. · 2014 to 2023
$4.0M
Niche support of human intestinal stem cellsU01DK103141 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SPENCE, JASON · 2014 to 2023
$3.9M
Training in Basic and Translational Digestive SciencesT32DK094775 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JOHN Y KAO, LINDA C. SAMUELSON · 2012 to 2026
$3.6M
Limited Competition for the Continuation of the Intestinal Stem Cell Consortium Coordinating CenterU24DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2019 to 2023
$2.3M
Human Endocrine Cell DevelopmentR01DK092456 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI WELLS, JAMES M · 2012 to 2016
$2.3M
KLF5 regulation of intestinal development and stem cell homeostasis.R01DK092306 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI SHROYER, NOAH FREEMAN · 2011 to 2014
$1.6M
Mechanisms of Intestinal Stem Cell Expansion Following ResectionR01DK083325 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HELMRATH, MICHAEL A. · 2009 to 2013
$1.5M
NCI NIH HHS CA142826NCI NIH HHS R01 CA142826NCRR NIH HHS UL1 RR026314NCRR NIH HHS UL1RR026314NIDDK NIH HHS DK092306NIDDK NIH HHS DK092456NIDDK NIH HHS DK094775NIDDK NIH HHS DK36729NIDDK NIH HHS K01 DK091415NIDDK NIH HHS K01DK091415NIDDK NIH HHS P30 DK034933NIDDK NIH HHS P30DK034933NIDDK NIH HHS P30 DK078392NIDDK NIH HHS R01 DK036729NIDDK NIH HHS R01 DK083325NIDDK NIH HHS R01DK083325NIDDK NIH HHS R01 DK092306NIDDK NIH HHS R01 DK092456NIDDK NIH HHS R01 DK098350NIDDK NIH HHS R01DK098350NIDDK NIH HHS T32 DK094775NIDDK NIH HHS U01 DK085532NIDDK NIH HHS U01 DK103117NIDDK NIH HHS U01 DK103141NIDDK NIH HHS U24 DK085532NINDS NIH HHS U18NS080815
6 · The paper itself

Abstract

Differentiation of human pluripotent stem cells (hPSCs) into organ-specific subtypes offers an exciting avenue for the study of embryonic development and disease processes, for pharmacologic studies and as a potential resource for therapeutic transplant. To date, limited in vivo models exist for human intestine, all of which are dependent upon primary epithelial cultures or digested tissue from surgical biopsies that include mesenchymal cells transplanted on biodegradable scaffolds. Here, we generated human intestinal organoids (HIOs) produced in vitro from human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) that can engraft in vivo. These HIOs form mature human intestinal epithelium with intestinal stem cells contributing to the crypt-villus architecture and a laminated human mesenchyme, both supported by mouse vasculature ingrowth. In vivo transplantation resulted in marked expansion and maturation of the epithelium and mesenchyme, as demonstrated by differentiated intestinal cell lineages (enterocytes, goblet cells, Paneth cells, tuft cells and enteroendocrine cells), presence of functional brush-border enzymes (lactase, sucrase-isomaltase and dipeptidyl peptidase 4) and visible subepithelial and smooth muscle layers when compared with HIOs in vitro. Transplanted intestinal tissues demonstrated digestive functions as shown by permeability and peptide uptake studies. Furthermore, transplanted HIO-derived tissue was responsive to systemic signals from the host mouse following ileocecal resection, suggesting a role for circulating factors in the intestinal adaptive response. This model of the human small intestine may pave the way for studies of intestinal physiology, disease and translational studies.

Indexed as

Models, BiologicalAdultAnimalsCecumCell LineHumansIleumIntestine, SmallIn Vitro TechniquesMice, Inbred NODMice, SCIDOrganoidsPluripotent Stem Cells

Identifiers

PMID25326803
PMCPMC4408376
OpenAlexW2031522785

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.