Synergistic applications of artificial intelligence and organoid technology in gastric precancerous lesion research: Mechanisms, translation, and challenges

Table 5 Major limitations and challenges of organoid models in gastric precancerous lesion research

Category	Specific challenge/issue	Supporting evidence/explanation	Ref.
Research focus	Relative scarcity of precancerous lesion models	Current studies predominantly focus on advanced gastric cancers, with limited research on constructing organoid models for atrophic gastritis and intestinal metaplasia	[17]
Model fidelity and complexity	Lack of tumor microenvironment (TME) components	Existing models primarily consist of epithelial cells and lack critical TME components (immune cells, stromal cells, intratumoral microbiota), unable to fully replicate essential interactions (e.g., with H. pylori)	[16-18,54,64,65]
	Inability to recapitulate systemic physiology	Constraints in fully recapitulating vascular systems, innervation, and interactions with systemic physiological processes	[17]
Standardization and reproducibility	Lack of standardized protocols	Significant challenges exist in organoid culture methodologies, analytical techniques, and data interpretation, compromising reproducibility and reliability	[17,67]
	Model qualification gap	Absent standardized qualification processes undermine confidence in models' physiological relevance	[55]
Scalability and practicality	Challenges in scalability and cost	Limitations in scalability, reproducibility, cost-effectiveness, and time efficiency. Relatively long culture cycle, variable success rates, batch-to-batch variations, and high costs limit large-scale application	[54,55,68-70]
Model validation and comparison	Unclear representativeness	Whether organoids fully represent all characteristics of the original lesional tissue requires further validation. Inconsistent culture success rates and extended cycles are current drawbacks	[15]
	Lack of comparative studies	Notable absence of head-to-head studies comparing organoids against more established models (e.g., animal models, ALI models) to clarify their unique advantages and optimal applications	[6,67]
Clinical translation	Limited direct clinical evidence	Organoids are primarily used in basic research. Direct evidence for application in clinical diagnostics (e.g., predicting progression risk) remains scarce, and the technology remains distant from direct clinical implementation	[17,61,62,67]

ALI: Air-liquid interface; H. pylori: Helicobacter pylori.