ArticlePloS one2014
Type I collagen as an extracellular matrix for the in vitro growth of human small intestinal epithelium.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 120 citations in OpenAlex.
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- Developing a protocol to counteract spontaneous in vitro activation of intestinal fibroblasts using design of experiments.npj biomedical innovations · 2026Article
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- Developing a Cell Culture Protocol to Induce Quiescence in Intestinal Fibroblasts Using Design of Experiments Statistical Optimization.Research square · 2025Article
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- Half-Pipe Melt Electrowritten Scaffolds Support Engineering of an Immunocompetent Hydrogel-Embedded Intestine-on-a-Chip.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Vitamin E Enhances Immune Function and the Intestinal Histological Structure by Regulating theBiology · 2025Article
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- Cancer patient-derived organoids: Novel models for the study of natural products.International journal of biological sciences · 2025Review
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- Polymer design of microwell hydrogels influences epithelial-mesenchymal interactions during human bronchosphere formation.Advanced nanobiomed research · 2025Article
- Developments in gastrointestinal organoid cultures to recapitulate tissue environments.Frontiers in bioengineering and biotechnology · 2025Review
- Listen to Your Gut: Key Concepts for Bioengineering Advanced Models of the Intestine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Graphene Oxide Nanoparticles and Organoids: A Prospective Advanced Model for Pancreatic Cancer Research.International journal of molecular sciences · 2024Review
- Engineered organoids for biomedical applications.Advanced drug delivery reviews · 2023Review
- Recent advances in lung organoid development and applications in disease modeling.The Journal of clinical investigation · 2023Review
- 3D in vitro hydrogel models to study the human lung extracellular matrix and fibroblast function.Respiratory research · 2023Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundWe previously reported in vitro maintenance and proliferation of human small intestinal epithelium using Matrigel, a proprietary basement membrane product. There are concerns over the applicability of Matrigel-based methods for future human therapies. We investigated type I collagen as an alternative for the culture of human intestinal epithelial cells.
methodsHuman small intestine was procured from fresh surgical pathology specimens. Small intestinal crypts were isolated using EDTA chelation. Intestinal subepithelial myofibroblasts were isolated from a pediatric sample and expanded in vitro. After suspension in Matrigel or type I collagen gel, crypts were co-cultured above a confluent layer of myofibroblasts. Crypts were also grown in monoculture with exposure to myofibroblast conditioned media; these were subsequently sub-cultured in vitro and expanded with a 1∶2 split ratio. Cultures were assessed with light microscopy, RT-PCR, histology, and immunohistochemistry.
resultsCollagen supported viable human epithelium in vitro for at least one month in primary culture. Sub-cultured epithelium expanded through 12 passages over 60 days. Histologic sections revealed polarized columnar cells, with apical brush borders and basolaterally located nuclei. Collagen-based cultures gave rise to monolayer epithelial sheets at the gel-liquid interface, which were not observed with Matrigel. Immunohistochemical staining identified markers of differentiated intestinal epithelium and myofibroblasts. RT-PCR demonstrated expression of α-smooth muscle actin and vimentin in myofibroblasts and E-Cadherin, CDX2, villin 1, intestinal alkaline phosphatase, chromogranin A, lysozyme, and Lgr5 in epithelial cells. These markers were maintained through several passages.
conclusionType I collagen gel supports long-term in vitro maintenance and expansion of fully elaborated human intestinal epithelium. Collagen-based methods yield familiar enteroid structures as well as a new pattern of sheet-like growth, and they eliminate the need for Matrigel for in vitro human intestinal epithelial growth. Future research is required to further develop this cell culture system for tissue engineering applications.
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