In Vitro Models for Intestinal Epithelial Function

In vitro models of the intestinal epithelium have evolved from simple monolayers of immortalised cell lines to sophisticated three-dimensional co-culture and microfluidic platforms that recapitulate key aspects of human gut physiology. Traditional two-dimensional cultures using enterocyte-like Caco-2 cells, mucus-producing HT29-MTX cells and monocyte-derived macrophages have long served to investigate nutrient transport, barrier integrity and basic host–microbe interactions. More recently, organoids generated from adult stem cells provide self-organising mini-guts that preserve cellular diversity and region-specific functions. Organ-on-chip devices integrate dynamic flow, shear stress and peristaltic-like motions to replicate luminal forces, while hydrogel scaffolds and bioprinting techniques support sustained three-dimensional culture with villus-like architecture. These advances reduce reliance on animal models, enable patient-specific investigations and accelerate screening of drugs, nutraceuticals and microbiome-targeted therapies in a globally relevant context.

Research from Nature Portfolio

A seminal three-dimensional co-culture system employed a thermoresponsive hydrogel scaffold to sustain Caco-2 and HT29-MTX cells under dynamic flow for up to 12 weeks. The model developed finger-like villus projections and maintained markers of epithelial differentiation. Following treatment with interleukin-1β, tumour necrosis factor-α and hypoxia, alterations in tight junction protein ZO-1, increased mucin production and caspase-3 activation were observed, faithfully reproducing key features of chronic inflammatory bowel disease. This platform demonstrated robust measurement of barrier function, enzymatic activity and cytokine secretion, offering a physiologically relevant tool for long-term studies of intestinal inflammation and for the evaluation of anti-inflammatory interventions.

In Vitro Models for Intestinal Epithelial Function publication trend

The graph below shows the total number of articles in in vitro models for intestinal epithelial function across all publications each year (not limited to Nature Index journals).

Technical terms

Organoid: A self-organising three-dimensional cell culture derived from stem cells that mimics key structural and functional features of the intestinal epithelium.

Co-culture: An in vitro system in which two or more cell types are grown together to model interactions between different cell populations.

Hydrogel scaffold: A hydrated polymer network used as a three-dimensional support for cell growth, enabling tissue-like architecture and prolonged culture.

Transepithelial electrical resistance (TEER): A measure of ionic conductance across an epithelial layer, used to quantify barrier integrity.

Tight junctions: Protein complexes located at the apical region of epithelial cells that control paracellular permeability and maintain barrier function.

References

1. Complexification of In Vitro Models of Intestinal Barriers, A True Challenge for a More Accurate Alternative Approach. International Journal of Molecular Sciences (2023).
2. Development of an in vitro co-culture model to mimic the human intestine in healthy and diseased state. Toxicology in Vitro (2017).
3. Long-term in vitro 3D hydrogel co-culture model of inflammatory bowel disease. Scientific Reports (2019).
4. Development of an Advanced Multicellular Intestinal Model for Assessing Immunomodulatory Properties of Anti-Inflammatory Compounds. Frontiers in Pharmacology (2021).
5. Current Perspectives on Gastrointestinal Models to Assess Probiotic-Pathogen Interactions. Frontiers in Microbiology (2022).