Exploring intestinal ischemia-reperfusion injury through human-to-organoid disease modeling and biomarker-driven clinical studies

Intestinal ischemia is a life-threatening condition characterized by reduced blood flow to the intestine, often caused by a blood clot. Without timely treatment, this leads to severe intestinal damage and inflammation of the intestine. The lack of reliable diagnostic tests, combined with vague symptoms experienced by patients, makes early recognition of the condition difficult, thereby lowering survival rates. Prompt intervention to restore blood flow to the intestine is crucial but can temporarily worsen intestinal damage, a phenomenon known as intestinal ischemia-reperfusion injury. Much remains unknown about the complex biological mechanisms underlying this injury, which limits treatment options.
This dissertation describes a clinical study investigating the suitability of new biomarkers for a rapid and reliable diagnosis of intestinal ischemia. Additionally, research was conducted into the mechanisms contributing to ischemia-reperfusion injury, using an experimental model in humans and ‘mini-guts’ in a petri dish (so called organoids), combined with innovative imaging techniques.