Inflammatory bowel disease (IBD) is a lifelong chronic inflammatory condition of the gastrointestinal tract (GIT), with incidence and prevalence increasing worldwide. It is considered a complex, multifactorial disease with no cure. Even though large progress has been made in recent years, current therapies are far from satisfactory, and show extreme variability of outcomes due to patient heterogeneity. The traditional therapy consists of anti-inflammatories, corticosteroids, antibiotics, and immunomodulatory drugs. This non-specific immunosuppression guarantees disease-control in some patients although the long-term use of these drugs is correlated with a significant number of therapy-associated complications and side-effects. A dramatic improvement in disease management was achieved by the introduction of biological agents targeting pro-inflammatory cytokines such as anti-TNF-α. Despite the revolutionary impact of these agents in IBD disease management, treatments such as anti-TNF-α do show several drawbacks – for example, up to 50% of patients do not respond at all or eventually lose response. This variability in clinical outcome is reflecting the variability of individuals due to different genetics, life style and inflammatory state. Therefore, there is a need to define the specific inflammatory state of a given patient, considering individual complications and develop new in-vitro systems and biomarkers that predict drug responsiveness and allow developing patient-specific treatment
In this thesis, different in-vitro models were developed addressing different aspects and compartments of IBD pathology including the enteric nervous system, the ECM component fibrillin-1, as well as patient-derived, three dimensional short-term and long-term cultures that will bring us a step closer towards personalized medicine
