Fraunhofer Institute for Toxicology and Experimental Medicine
Approximately seven million people worldwide suffer from inflammatory bowel diseases (IBD). Those affected are severely impaired by symptoms such as abdominal pain, diarrhea, bleeding, and weight loss, and additionally face an increased risk of colorectal cancer as well as cardiovascular and respiratory diseases. As IBD typically begins in early adulthood and progresses over time, it also represents a substantial burden on healthcare systems and the economy.
At the same time, only a small proportion of patients achieve sustained clinical remission with currently available therapies, highlighting the ongoing need for new drugs and personalized treatment approaches. In this context, human-relevant test systems are becoming increasingly important for the preclinical evaluation of new therapeutics, particularly immunotherapies. In recent years, Fraunhofer ITEM has therefore established human intestinal models that enable a better understanding of the immunological mechanisms underlying IBD and allow targeted therapeutic options to be tested directly in human tissue (Grieger et al., 2025, DOI: 10.1002/eji.70013).
Central to this work are precision-cut intestinal slices (PCIS): thin, viable tissue slices derived from the human intestine. They contain tissue-resident immune cells and respond to immunological stimuli. Recent studies show that PCIS from IBD patients retain characteristic disease features and exhibit specific cytokine responses upon stimulation with mitogens, which can be modulated by pharmacological interventions. In addition, the influence of microbial mediators on local tissue responses can be investigated. Combining PCIS with classical cell culture models enables the analysis of functional aspects such as the intestinal barrier.
Overall, this approach provides a unique human test platform for investigating pharmacological mechanisms of action and immunoregulatory networks in the human intestine, while at the same time contributing to the reduction of animal experiments in line with the 3Rs principle.
