Gastrointestinal organs and organoids-on-a-chip: advances and translation into the clinics

Abstract

Microfluidic organs and organoids-on-a-chip models of human gastrointestinal systems have been established to recreate adequate microenvironments to study physiology and pathophysiology. In the effort to find more emulating systems and less costly models for drugs screening or fundamental studies, gastrointestinal system organoids-on-a-chip have arisen as promising pre-clinical in vitro model. This progress has been built on the latest developments of several technologies such as bioprinting, microfluidics, and organoid research. In this review, we will focus on healthy and disease models of: human microbiome-on-a-chip and its rising correlation with gastro pathophysiology; stomach-on-a-chip; liver-on-a-chip; pancreas-on-a-chip; inflammation models, small intestine, colon and colorectal cancer organoids-on-a-chip and multi-organoids-on-a-chip. The current developments related to the design, ability to hold one or more ‘organs’ and its challenges, microfluidic features, cell sources and whether they are used to test drugs are overviewed herein. Importantly, their contribution in terms of drug development and eminent clinical translation in precision medicine field, Food and Drug Administration approved models, and the impact of organoid-on-chip technology in terms of pharmaceutical research and development costs are also discussed by the authors.

The application of organoids in colorectal diseases

“…These miniature organ models can be cultivated from a small number of cells or tissue samples and serve as effective tools for disease modeling and drug screening. They also hold potential for therapeutic interventions by enabling the reversal of pathogenetic mutations responsible for mutation-induced diseases ( Carvalho et al, 2023 ). Using patients’ cells to construct organoids provides new possibilities for formulating personalized diagnosis and treatment programs ( Betge and Jackstadt, 2023 ).…”

Cholinergic Mechanisms in Gastrointestinal Neoplasia

“…There has been rapid innovation in developing system-on-a-chip technologies, essentially co-culturing organoids with other pre-selected cell lines, such as tumor-associated macrophages, fibroblasts, and gut microbiota, making it possible to model more complex tumor environments [66]. As reviewed elsewhere, this is being applied to research on the human gut microbiome and cancers of the stomach, liver, pancreas, and colon [67].…”

Organoids in gastrointestinal diseases: from bench to clinic

“…The past few years have witnessed significant advancements in organoid‐related techniques, including different cultivation methods and strategies for enhancing cellular components to better emulate native organ structures. 16 , 17 , 18 , 19 These achievements have greatly contributed to the progress of biomedical research by enabling disease modeling, elucidating pathogenic mechanisms, and exploring therapeutic strategies. In order to get a comprehensive understanding of the current progression, it is crucial to summarize and analyze existing findings at the forefront of this field.…”