ArticleCell stem cell2025
Coordinated differentiation of human intestinal organoids with functional enteric neurons and vasculature.
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Article in Cell stem cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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30citing papers in PubMed, 1 pooled it
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Guiding Principles: Reporting Elements for Gastrointestinal Organoid Research.Cellular and molecular gastroenterology and hepatology · 2026Guideline
- Organoids: Current Applications and Future Directions.MedComm · 2026Review
- Phenotypic switching of gastrointestinal smooth muscle cells and the regulatory role of macrophages: a literature review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Endodermal Organoids Along Two Axes: Single-Organ Fidelity, Inter-Organ Reconstruction, and the Unbuilt Gut-Lung Frontier.Stem cell reviews and reports · 2026Review
- Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026Review
- Advances in vascularized organoids.Chinese medical journal · 2026Review
- Mapping mesenchymal diversity in the human small intestine and organoids.Nature cell biology · 2026Article
- Enabling Technologies in Vascular Biology: Microphysiological Systems, Organoids, and Beyond.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Mesoscale maladaptation in disease organoids.Disease models & mechanisms · 2026Article
- Generation of biologically responsive colon-like intestinal tissue patches from human induced pluripotent stem cells using a rapid co-differentiation platform.Stem cell research & therapy · 2026Article
- International Forum on Visceral Myopathy 2024: Advances in the Knowledge of the Disease.Neurogastroenterology and motility · 2026Review
- Integrating Human Intestinal Organoids into FDA's New Approach Methodologies for Drug Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Progress in human intestinal organoid research: applications to acute gastroenteritis viruses.Stem cell research & therapy · 2026Review
- The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026Article
- Organoid Technology as a Promising Frontier in Organ Transplantation and Regenerative Medicine.International journal of stem cells · 2026Review
- Organoids for disease modeling and treatment: state-of-the-art.Experimental hematology & oncology · 2026Review
- Early life nutritional imbalance impairs colonic epithelial regeneration through gut microbiota dysbiosis and metabolic suppression.The ISME journal · 2026Article
- Construction of Vascularized Intestinal Organoids Based on Scaffolds, Hydrogels, and 3D Printing Technologies and Their Applications in Drug Delivery.International journal of nanomedicine · 2026Review
- Organoid research: new concepts and new technologies.Burns & trauma · 2026Review
- Gut microbiota-M cell co-culture in inflammatory bowel disease and its therapeutic potential in organoid platforms.Frontiers in pharmacology · 2026Review
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Authors and funding
25 authors.
Charlie J ChildsDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.
Holly M PolingCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Biomedical Engineering, University of Cincinnati College of Engineering and Applied Science, Cincinnati, OH, USA.
Kevin ChenHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Yu-Hwai TsaiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Angeline WuDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Abigail VallieGraduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Madeline K EikenDepartment of Biomedical Engineering, University of Michigan and University of Michigan College of Engineering, Ann Arbor, MI, USA.
Sha HuangDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Caden W SweetDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Ryan SchreinerHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY, USA.
Zhiwei XiaoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Ryan C SpencerDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Samantha A ParisDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Ansley S ConcholaGraduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Jonathan W VillanuevaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Meghan F AndermanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Emily M HollowayDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Akaljot SinghCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Roman J GigerDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Maxime M MaheCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Université de Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Nantes, France.
Claudia LoebelDepartment of Biomedical Engineering, University of Michigan and University of Michigan College of Engineering, Ann Arbor, MI, USA; Department of Materials Science and Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA.
Michael A HelmrathCenter for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Katherine D WaltonDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Shahin RafiiHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Jason R SpenceDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA; Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan and University of Michigan College of Engineering, Ann Arbor, MI, USA. Electronic address: spencejr@umich.edu.
Funding
Michigan Institute for Clinical and Health Research (MICHR)UM1TR004404 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Julie C Lumeng · 2023 to 2026
$39.8MStem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4MUniversity of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5MConsortium on Intestinal Regeneration and Fetal Reversion: from Atlas to TherapyRC2DK140862 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI SARAH E BLUTT, DARIO BOFFELLI · 2024 to 2026
$6.0MCellular and Molecular Biology at MichiganT32GM145470 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Chadwick Brenner · 2022 to 2026
$4.1MNiche support of human intestinal stem cellsU01DK103141 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SPENCE, JASON · 2014 to 2023
$3.9MMechanisms of Hedgehog Regulation of Intestinal Villus MorphogenesisR01DK121166 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WALTON, KATHERINE DEMPSEY · 2019 to 2023
$1.8MHuman iPSC intestine mimetics with integrated mesenchymal, endothelial and enteric nervous tissueR01DK137806 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jason Spence · 2024 to 2026
$1.5MInvestigating the Role of Epiregulin During Human Intestinal DevelopmentF31DK136196 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHILDS, CHARLIE · 2023 to 2024
$96kNCATS NIH HHS UM1 TR004404NIDDK NIH HHS F31 DK136196NIDDK NIH HHS P30 DK034933NIDDK NIH HHS P30 DK078392NIDDK NIH HHS R01 DK121166NIDDK NIH HHS R01 DK137806NIDDK NIH HHS RC2 DK140862NIDDK NIH HHS U01 DK103141NIGMS NIH HHS T32 GM145470
Abstract
Human intestinal organoids (HIOs) derived from human pluripotent stem cells co-differentiate both epithelial and mesenchymal lineages in vitro but lack important cell types such as neurons, endothelial cells, and smooth muscle, which limits translational potential. Here, we demonstrate that the intestinal stem cell niche factor, EPIREGULIN (EREG), enhances HIO differentiation with epithelium, mesenchyme, enteric neuroglial populations, endothelial cells, and organized smooth muscle in a single differentiation, without the need for co-culture. When transplanted into a murine host, HIOs mature and demonstrate enteric nervous system function, undergoing peristaltic-like contractions indicative of a functional neuromuscular unit. HIOs also form functional vasculature, demonstrated in vitro using microfluidic devices and in vivo following transplantation, where HIO endothelial cells anastomose with host vasculature. These complex HIOs represent a transformative tool for translational research in the human gut and can be used to interrogate complex diseases as well as for testing therapeutic interventions with high fidelity to human pathophysiology.
Indexed as
Cell DifferentiationEnteric Nervous SystemIntestinesNeuronsOrganoidsAnimalsEndothelial CellsEpiregulinHumansMicePluripotent Stem CellsEpiregulindirected differentiationenteric neruonHIOhuman intestinal organoidsintestineorganoidspluripotentstem cellsvasculature
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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.