PhD defence C. (Carin) Biel

Precision-cut intestinal slices and intestinal fibrosis

The epithelial layer is the main barrier in the intestine and is responsible for, among other things, the uptake of nutrients. In this thesis, we characterized the epithelial layer and showed that the epithelial layer of mouse, rat and human precision-cut intestinal slices (PCIS) is intact after preparation of the PCIS but, does not stay intact during culture, as shown by deterioration of the histological appearance, and loss of specific cell types. We show that using specific growth factors, the epithelial integrity and the viability of PCIS can be prolonged.

Secondly, we investigated the role of matrix metalloproteinases (MMPs) in intestinal fibrosis. Intestinal fibrosis is a complication of inflammatory bowel disease (IBD). Based on a literature review, MMP-12 and TIMP-1 expression was evaluated in intestinal tissue from control, and IBD patients. We found increased expression of both proteins in all intestinal layers of IBD patients. Lastly, we explored the differences in fibrogenesis in the mucosa and muscularis PCIS. We found different expression patterns of fibrosis related genes and proteins upon culture in the mucosa and muscularis, in which the muscularis had a more pronounced fibrosis profile.

This thesis contributes to better understanding of culture induced changes in PCIS. Moreover, we showed the (un)known role of MMPs in intestinal fibrosis and how PCIS could contribute to a better understanding of intestinal fibrogenesis. With this thesis we paved a way for the future use of PCIS in pharmacokinetic, toxicology, drug efficacy studies, and the use of PCIS for studying intestinal fibrosis ex vivo.