Patient-derived organoids for therapy personalization in inflammatory bowel diseases

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestinal tract that have emerged as a growing problem in industrialized countries. Knowledge of IBD pathogenesis is still incomplete and the most widely-accepted interpretation considers as determinants of IBD genetic factors, environmental stimuli, uncontrolled immune responses and altered intestinal microbiota composition, leading to disfunction of the intestinal epithelial functions. In vitro models commonly used to study the intestinal barrier do not fully reflect the proper intestinal architecture and human diseases. An important innovation is represented by organoids, 3D in vitro cell structures derived from stem cells that can self-organize into functional organ-specific cell types. Organoids may be generated from pluripotent stem cells or adult stem cells, which can be isolated from the intestinal tissue of IBD patients and therefore retain their genetic and transcriptomic profile. These models are powerful pharmacological tools to better understand IBD pathogenesis, to study the mechanisms of action on the epithelial barrier of drugs already used in the treatment of IBD, and to evaluate novel target-directed molecules which could improve therapeutic strategies. The aim of this review is to illustrate the potential use of organoids for therapy personalization by focusing on the most significant advances in IBD research achieved through the use of adult stem cells-derived intestinal organoids.