- Understanding Helicobacter pylori infection and pathogenesis has required a diverse array of experimental models, ranging from simple cell cultures to complex in vivo systems.
- These models have been crucial for dissecting bacterial adhesion, CagA translocation, host signaling responses, immune evasion, and disease outcomes such as gastritis and gastric cancer.
In Vitro Cell Line Models
- The earliest and most widely used models involve immortalized epithelial cell lines, particularly of gastric or epithelial origin.
- The AGS cell line, derived from human gastric adenocarcinoma, remains the most commonly used due to its high susceptibility to CagA translocation and strong signaling responses. However, AGS cells lack epithelial polarity and E-cadherin expression, limiting their utility in studying junctional biology.
- To address this, more polarized epithelial cell lines such as NCI-N87 (gastric origin), MDCK (canine kidney), and Caco-2 (intestinal origin) have been employed to study tight junction dynamics, epithelial integrity, and barrier function.
- Each of these lines offers unique strengths: NCI-N87 cells retain gastric differentiation markers; MDCK cells excel in polarity and TEER measurements; and Caco-2 cells are useful for barrier-related assays and long-term differentiation studies.
Primary Human Gastric Epithelial Cells
- While less commonly used due to challenges in availability and culture conditions, primary human gastric epithelial cells provide a more physiologically accurate model of the gastric mucosa.
- These cells preserve native expression of surface proteins, junctional complexes, and mucin secretion, making them ideal for studying H. pylori adhesion, toxin interaction, and innate immune responses. However, their limited lifespan and inter-donor variability restrict their widespread use.
3D Gastric Organoids and Gastric Glands
- In recent years, gastric organoids or gastroids derived from human pluripotent stem cells or primary gastric tissue have revolutionized H. pylori research. These 3D cultures recapitulate the architecture and cellular diversity of the gastric epithelium, including mucus-producing cells, pit cells, and progenitor zones.
- H. pylori infection of organoids has revealed key insights into niche colonization, host cell polarity, stem cell targeting, and epithelial remodeling.
- Co-culture of organoids with immune or stromal cells is an exciting area of development, potentially enabling a full mucosal microenvironment model.
Transwell and Air-Liquid Interface Systems
- To mimic the apical exposure of gastric mucosa, epithelial cells are often grown on Transwell inserts, allowing access to both apical and basolateral compartments.
- These systems are crucial for modeling CagA injection, tight junction disruption, cytokine secretion, and immune cell transmigration.
- Air-liquid interface cultures, particularly of gastric or intestinal origin, further enhance differentiation and mucus production, mimicking the luminal side of the epithelium more effectively.
Animal Models
- Mouse models have been widely used to study H. pylori colonization, immune response, and gastric pathology.
- Though mice do not naturally host H. pylori, infection with adapted strains (e.g., SS1, PMSS1) can reproduce chronic gastritis and epithelial changes.
- Mongolian gerbils, with their susceptibility to ulceration and gastric carcinoma, are useful for long-term studies of carcinogenesis.
- Transgenic and knockout mice (e.g., IL-1β, TLRs, NF-κB pathway components) provide mechanistic insights into host immune signaling. However, species-specific differences in immune responses and gastric physiology must be considered when extrapolating findings.
Humanized Mouse Models
- To overcome limitations of traditional animal models, humanized mice have been developed by engrafting human gastric tissue or immune systems into immunodeficient mice.
- These models offer a promising platform to study human-specific host–pathogen interactions, including H. pylori–CagA targeting of human proteins, and adaptive immune responses.
Ex Vivo Gastric Tissue Explants
- Human or animal gastric biopsies or explants provide a short-term ex vivo model that retains tissue architecture and cellular complexity.
- These models have been used to study early H. pylori colonization, immune cell recruitment, and epithelial changes under near-physiological conditions. However, they are technically demanding and limited in experimental duration.
