ArticleCellular and molecular gastroenterology and hepatology2018
Formation of Human Colonic Crypt Array by Application of Chemical Gradients Across a Shaped Epithelial Monolayer.
Article in Cellular and molecular gastroenterology and hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 186 citations in OpenAlex.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Recent advancements and limitations of intestinal organoids for clinical applications.Progress in biomedical engineering (Bristol, England) · 2026Review
- Geometrically Constrained Growth Factor Concentration Favors Enrichment of Goblet Cells and Mucus Formation.ACS biomaterials science & engineering · 2026Article
- Reducing the weaning impact in piglets with dietary fiber: the role of milled almond shells compared to wheat bran.Journal of animal science · 2026Article
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- A scalable long-termbioRxiv : the preprint server for biology · 2025Article
- Review
- Bioprinted Organoids: An Innovative Engine in Biomedicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host-microbe interactions.mSphere · 2025Review
- Patterned gastrointestinal monolayers with bilateral access as observable models of parasite gut infection.Nature biomedical engineering · 2025Article
- Imaging 3D cell cultures with optical microscopy.Nature methods · 2025Review
- Engineered Tissue Models to Decode Host-Microbiota Interactions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- A tunable human intestinal organoid system achieves controlled balance between self-renewal and differentiation.Nature communications · 2025Article
- Emerging technologies and current challenges in intratumoral microbiota research.Frontiers in cellular and infection microbiology · 2025Review
- Dietary and metabolic effects on intestinal stem cells in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Spatially defined microenvironment for engineering organoids.Biophysics reviews · 2024Review
- Intestinal organ chips for disease modelling and personalized medicine.Nature reviews. Gastroenterology & hepatology · 2024Review
- A Microphysiological System with an Anaerobic Air-Liquid Interface and Functional Mucus Layer for Coculture of Intestinal Bacteria and Primary Human Colonic Epithelium.Advanced materials interfaces · 2024Article
- A flexible strategy to fabricate trumpet-shaped porous PDMS membranes for organ-on-chip application.Biomicrofluidics · 2024Article
- Creation of a spatially complex mucus bilayer on an in vitro colon model.Scientific reports · 2024Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe successful culture of intestinal organoids has greatly enhanced our understanding of intestinal stem cell physiology and enabled the generation of novel intestinal disease models. Although of tremendous value, intestinal organoid culture systems have not yet fully recapitulated the anatomy or physiology of the in vivo intestinal epithelium. The aim of this work was to re-create an intestinal epithelium with a high density of polarized crypts that respond in a physiologic manner to addition of growth factors, metabolites, or cytokines to the basal or luminal tissue surface as occurs in vivo.
methodsA self-renewing monolayer of human intestinal epithelium was cultured on a collagen scaffold microfabricated with an array of crypt-like invaginations. Placement of chemical factors in either the fluid reservoir below or above the cell-covered scaffolding created a gradient of that chemical across the growing epithelial tissue possessing the in vitro crypt structures. Crypt polarization (size of the stem/proliferative and differentiated cell zones) was assessed in response to gradients of growth factors, cytokines, and bacterial metabolites.
resultsChemical gradients applied to the shaped human epithelium re-created the stem/proliferative and differentiated cell zones of the in vivo intestine. Short-chain fatty acids applied as a gradient from the luminal side confirmed long-standing hypotheses that butyrate diminished stem/progenitor cell proliferation and promoted differentiation into absorptive colonocytes. A gradient of interferon-γ and tumor necrosis factor-α significantly suppressed the stem/progenitor cell proliferation, altering crypt formation.
conclusionsThe in vitro human colon crypt array accurately mimicked the architecture, luminal accessibility, tissue polarity, cell migration, and cellular responses of in vivo intestinal crypts.
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