Gastric organoid/organ-on-a-chip platforms for disease modeling and personalized medicine: a review

Mechanical, structural, and physiological changes in the stomach underlie both short- and long-term gastric pathologies, most of which are influenced by disruptions of acid secretion, mucosal barrier integrity, motility, or immune responses. Species-specific distinctions limit the study of the pathophysiological state of the human stomach in preclinical animal models. Organoid and organ-on-a-chip (OoC) technologies are emerging tools for recapitulating the compositional and functional properties of native gastric tissue, thus revolutionizing research in gastric health and disease as well as drug screening. The review summarizes recent progress in the development of organoids to model gastric development and disease states to investigate their underlying mechanisms and evaluate associated treatments. Furthermore, microfluidic-based OoC models of the human stomach with an epithelial lining that interfaces with adjacent tissues (including the endothelium and stroma) are described for their increased physiologic relevance owing to the presence of fluid flow and peristalsis-like motion. Finally, we discuss the engineering challenges of the present organoid/OoCsystems, including cell sourcing, experimental throughput, and scalable fabrication, followed by highlighting the future opportunities regarding the optimization of in vitro gastric models for studying gastric pathophysiology and developing personalized therapeutic agents.