Gastrointestinal tract, its pathophysiology and in-vitro models: A “quick” reference guide to translational studies

Abstract

The gastrointestinal (GI) tract is essential for digestion, absorption, excretion, and protection, supported by a diverse microbial ecosystem. Traditional in-vitro models often fall short in capturing the physiological complexity of the GI tract, limiting their translational applications. A comprehensive approach is needed to bridge the gap between simple cell cultures and more complex systems used in translational research. This review explores the limitations of conventional two-dimensional cell cultures and emphasizes the emerging use of three-dimensional and microfluidic systems that better replicate the GI tract’s structure and functions. It highlights the importance of incorporating patient-derived cells and engineered microenvironments to enhance model relevance and support personalized medicine. The review also discusses advanced fabrication techniques such as micro-extrusion and laser-assisted bioprinting, which enable the creation of sophisticated tissue models capable of simulating critical GI processes, including molecular transport, peristalsis, and liver coupling. Advancing the complexity of in-vitro systems will help replicate the GI tract’s interactions and physiological phenomena, thus improving the translational potential of GI research. This review provides valuable insights into the advancements and challenges in GI modeling, serving as a comprehensive guide for developing models that bridge the gap between basic cell cultures and clinically relevant systems.

Keywords: Cell line; Tumour cell line; In vitro techniques; Gastrointestinal tract; Organoids; Organ-on-chip

Core Tip: This review highlights the need for advanced in-vitro models to better replicate the gastrointestinal (GI) tract’s complexity for translational research. It compares the evolution from conventional 2-dimensional cultures toward 3-dimensional and microfluidic systems. Key advancements include the use of patient-derived cells, engineered microenvironments, and bioprinting techniques like micro-extrusion and laser-assisted printing. These technologies enable modeling of essential processes such as peristalsis, molecular transport, and liver coupling. By enhancing physiological relevance, these models support personalized medicine and improve the predictive power of preclinical GI research.