Tarm-organoider fra præmature grise som in vitro model til forskning i nekrotiserende enterokolitis

Anders Brunse, Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen

Infants born preterm have a high risk of developing necrotizing enterocolitis (NEC), a life-threatening inflammation in the intestine associated with high mortality. Currently, no effective treatment is available, and surgery is often required to remove the affected tissue. Preterm piglets are applied as model of this disease, as they physiologically and developmentally resemble human infants and develop the same inflammatory state in the intestine as observed in NEC. The intestinal inflammation develops rapidly and can progress to a great extent of suffering for the inflicted animals, necessitating the use of methods without experimental animals.

Cell cultures based on single cell types are often not sufficient to model a complex disease such as NEC. Newer technology enables the culture of tissue from stem cells as miniature organs (organoids), which to a higher extent can represent the range of cells present in the intestine, and retains the inflammatory status from the original tissue. This makes intestinal organoids essential as an alternative tool in NEC research. However, the hitherto established models are restricted, as mice-derived organs are not preterm, and organoids from humans are difficult to obtain tissue for, and display differences in age and health status.

This project focuses on the culture of intestinal organoids from preterm piglets with and without NEC, cultured from tissue of piglets already included in existing studies. With this model, we can readily compare with the human intestine, and simultaneously affect contributing factors such as gestational age, nutrition and microbial colonization within the intestine. This project will contribute to reduce the number of experimental animals and increase the quality of research within NEC.

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