Modeling inflammation and inflammatory diseases in organoids.

INTRODUCTION: Organoids are 3D cellular structures that self-establish from stem cells and faithfully recapitulate key features of the tissue of interest. Organoids have emerged as powerful tools for disease modeling by maintaining pathology- and patient-specific characteristics, offering a highly valuable substitute for traditional cellular and animal models that often lack translational accuracy to model complex in vivo disease conditions. Despite its strong power, organoid cultures do not reconstruct the in vivo inflammatory microenvironment and thus do not maintain the imposed inflammatory state, making it challenging to model inflammation-linked diseases. SOURCE OF DATA: PubMed was used as database and source of information. AREAS OF AGREEMENT: Organoids represent powerful tools to unravel disease mechanisms and eventually screen and identify new therapeutic approaches. AREAS OF CONTROVERSY: Organoid models represent reliable but still reductionist representations of the in vivo tissue/organ, lacking the complex cell composition. Co-cultures with microenvironmental cell types or nearby impacting signaling factors are required to recapitulate the full disease phenotype, including the inflammatory state of the tissue. GROWING POINTS: To obtain more representative inflammatory disease research models, exposure of organoids to inflammatory stimuli such as cytokines and co-cultures with immune cells or microbiota are being established. AREAS TIMELY FOR DEVELOPING RESEARCH: Implementation of advanced cellular complexity and inflammation in organoid models will enable the study of inflammatory disease-driving mechanisms in an accurate and relevant setting, and result in advanced clinical translation of research findings.