Hesteetako organoideak, homeostasian eta gaixotasunean mikrobiota-immuno-epitelio interakzioak aztertzeko tresna

Abstract

In recent years, the interactions between the microbiota and the organism have been studied in depth from both homeostasis and disease perspectives, particularly with a focus on the gut. To better understand these interactions and reduce the use of animal models, in vitro models such as intestinal organoids have been developed. Intestinal organoids are three-dimensional (3D) structures structures composed of various types of intestinal cells that mimic intestinal functions and disease states. They can be generated in the lab by placing stem cells from adult tissue or pluripotent stem cells in an appropriate environment. They exhibit apical-basal polarity mirroring that of natural intestine and have the capacity to self-organize into complex 3D structures, simulating the dynamics of intestinal epithelium and disease processes. Co-culture systems in organoids enable the study of interactions between immune cells and epithelium, as seen in studies examining the effects of T lymphocytes on the intestine. Microorganism-epithelial interactions can also be investigated, though different protocols have been developed to access the apical side of organoids. Microorganisms may be introduced into organoids via microinjection, or the polarity of the organoids can be reversed to create "apical-out" organoids. One of the best alternatives, however, is the use of two-dimensional, 2D, intestinal monolayers, which allow simultaneous access to both apical and basolateral sides. The use of intestinal organoids provides specific insights into the mechanisms of damage and repair within the intestinal barrier, which is highly valuable in the search for new therapeutic targets. Research on intestinal organoids is therefore essential for uncovering the key elements of barrier function, especially in complex diseases such as inflammatory bowel disease, where the balance between the epithelium, microbiota, and immune cells is crucial.