Evidence map›Paper›PMID 34856121›Full record

ArticleCell stem cell2022

Functional human gastrointestinal organoids can be engineered from three primary germ layers derived separately from pluripotent stem cells.

Alexandra K Eicher, Daniel O Kechele, Nambirajan Sundaram, H Matthew Berns, Holly M Poling, Lauren E Haines, J Guillermo Sanchez, Keishi Kishimoto, Mansa Krishnamurthy, Lu Han and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

79 citing papers in PubMed, 127 citations in OpenAlex.

  1. Review
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  5. New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026
    Review
  6. Mesoscale maladaptation in disease organoids.Disease models & mechanisms · 2026
    Article
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19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 1 institution in 2 countries.

Alexandra K EicherCollege of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
Daniel O KecheleCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
Nambirajan SundaramCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
H Matthew BernsCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
Holly M PolingCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
Lauren E HainesCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
J Guillermo SanchezCollege of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
Keishi KishimotoDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; CuSTOM-RIKEN BDR Collaborative Laboratory, CCHMC, Cincinnati, OH 45229, USA; Laboratory for Lung Development, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe 650-0047, Japan.
Mansa KrishnamurthyCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Endocrinology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
Lu HanCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
Aaron M ZornCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
Michael A HelmrathCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.
James M WellsCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA; Division of Endocrinology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA. Electronic address: james.wells@cchmc.org.
Cincinnati Children's Hospital Medical Center · US

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
Project-3: Modeling EA/TEF in human organoidsP01HD093363 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI Wendy K Chung, Paul scot Kingma · 2017 to 2026
$16.2M
ENVIRONMETAL CARCINOGENESIS AND MUTAGENESIST32ES007250 · NIEHS · UNIVERSITY OF CINCINNATI · PI MILLER, WILLIAM E · 1988 to 2024
$11.9M
Intestinal Stem Cell Consortium Coordinating CenterU01DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2009 to 2018
$6.5M
Modeling diabetes using an integrated plate systemUH3DK119982 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI LEE, MOO-YEAL, WELLS, JAMES M · 2020 to 2022
$5.4M
Organoids as a Model System for Studying Gastrointestinal DiseaseU19AI116491 · NIAID · UNIVERSITY OF CINCINNATI · PI WEISS, ALISON A. · 2015 to 2019
$4.6M
Investigation of Regional Identity in Human Intestinal Stem CellsU01DK103117 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI HELMRATH, MICHAEL A. · 2014 to 2023
$4.0M
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
Modeling diabetes using an integrated plate systemUG3DK119982 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI LEE, MOO-YEAL, WELLS, JAMES M · 2018 to 2019
$1.7M
Generating Human Intestinal Organoids with an ENS.U18TR000546 · NCATS · CINCINNATI CHILDRENS HOSP MED CTR · PI WELLS, JAMES M · 2012 to 2014
$905k
Establishment of in vitro and in vivo models of human gastrointestinal organoids with a functional ENSU18EB021780 · NIBIB · CINCINNATI CHILDRENS HOSP MED CTR · PI HELMRATH, MICHAEL A., WELLS, JAMES M · 2015 to 2016
$622k
Development and Disease of the Human Proximal Enteric Nervous SystemF31DK118823 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI EICHER, ALEXANDRA · 2018 to 2020
$113k
NCATS NIH HHS U18 TR000546NIAID NIH HHS U19 AI116491NIBIB NIH HHS U18 EB021780NICHD NIH HHS P01 HD093363NIDDK NIH HHS F31 DK118823NIDDK NIH HHS P30 DK078392NIDDK NIH HHS U01 DK085532NIDDK NIH HHS U01 DK103117NIDDK NIH HHS U24 DK085532NIDDK NIH HHS UG3 DK119982NIDDK NIH HHS UH3 DK119982NIEHS NIH HHS T32 ES007250
6 · The paper itself

Abstract

Human organoid model systems lack important cell types that, in the embryo, are incorporated into organ tissues during development. We developed an organoid assembly approach starting with cells from the three primary germ layers-enteric neuroglial, mesenchymal, and epithelial precursors-that were derived separately from human pluripotent stem cells (PSCs). From these three cell types, we generated human antral and fundic gastric tissue containing differentiated glands surrounded by layers of smooth muscle containing functional enteric neurons that controlled contractions of the engineered antral tissue. Using this experimental system, we show that human enteric neural crest cells (ENCCs) promote mesenchyme development and glandular morphogenesis of antral stomach organoids. Moreover, ENCCs can act directly on the foregut to promote a posterior fate, resulting in organoids with a Brunner's gland phenotype. Thus, germ layer components that are derived separately from PSCs can be used for tissue engineering to generate complex human organoids.

Indexed as

OrganoidsPluripotent Stem CellsCell DifferentiationEndodermHumansNeural CrestBrunner's glandsenteric nervous systemgastrichuman pluripotent stem cellsmesenchymepatterningself-organizationtissue engineering

Identifiers

PMID34856121
PMCPMC8741755
OpenAlexW3214967637

What OpenQuestion holds

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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.