Model systems in gastroenterological research: From animal models to human organoids to the clinic

Abstract

Over the last few decades, various models have been established within gastroenterological research that have significantly contributed to a better understanding of the (patho)physiological processes of various gastrointestinal (GI) diseases (inflammation, organ injuries, carcinomas). This review will focus on such models including genetically engineered mouse models (GEMMs), xenografts, and organoid-based culture systems. GEMMs laid the foundation for successful modeling of such diseases. These have the decisive advantage that diseases can be assessed in their physiological environment and thus allow the examination of cell–cell communications of various cell types (epithelium, fibroblast, immune cells). However, the discrepancy between the genetic background of mice and humans reflected a pivotal disadvantage that could at least partially be circumvented by transplanting human cells into immunocompromised host animals. The time-consuming and labor-intensive generation of such xenograft models, however, considerably limits their usefulness for timely preclinical drug screenings. Thus, novel organoid-based human cell culture systems from adult stem cells or pluripotent stem cells are a promising human tool for modeling GI diseases. The first results already show their usefulness in the regulation of adult tissue homeostasis, regeneration, and tumor development. In addition, this system can be easily established in clinical diagnostics and thus enables real-time ex vivo pharmacotyping to develop personalized therapy strategies, particularly for cancer patients.