Research models to mimic Necrotizing Enterocolitis and Inflammatory Bowel Diseases: focus on Extracellular Vesicles action

: This review focuses on the crucial role of the Intestinal epithelium in maintaining intestinal homeostasis and its significance in the pathogenesis of necrotizing enterocolitis (NEC) and Inflammatory bowel diseases (IBD). NEC is a devastating neonatal disease, while IBD represents a global healthcare problem with increasing incidence. The breakdown of the intestinal barrier in neonates is considered pivotal in the development and progression of both disorders. This review provides an overview of the current state of in-vitro, ex-vivo and animal models to study epithelial injury in NEC and IBD, addressing pertinent questions that engage clinicians and researchers alike. Despite significant advancements in early recognition and aggressive treatment, no single therapy has been conclusively proven effective in reducing the severity of these disorders. Although early interventions have improved clinical outcomes, NEC and IBD continue to impose substantial morbidity, mortality and economic burdens on affected individuals and society. Consequently, exploring alternative therapeutic options capable of preventing and treating the sequelae of NEC and IBD has become a pressing necessity. In recent decades, extracellular vehicles (EVs) have emerged as a potential solution to modulate the pathogenic mechanism in these multifactorial and complex disorders. Despite the diverse array of proposed models, a comprehensive model to investigate and decelerate the progression of NEC and IBD remains to be established. To bridge the translational gap between preclinical studies and clinical applications, enhancements in the technical development of gut-on-a-chip models and EVs hold considerable promise.