Intestinal fibroblasts as therapeutic targets to treat Crohn’s disease

Inflammatory bowel diseases (IBD), e.g., Crohn’s disease and ulcerative colitis, are characterized by chronic and recurrent inflammation of the gut. Often diagnosed in young adulthood, IBD heavily impacts patients’ quality of life. The number of IBD patients is raising globally, currently affecting 0.5% and 1.3% of the population in the Netherlands and the US, respectively. Though multiple new drugs have become available in recent years, patients often are non-responsive, develop rather quickly therapy resistance and/or suffer from severe drug-induced side-effects. Recent findings indicate a key role of various subtypes of intestinal fibroblasts in different aspects of IBD, promoting either inflammation or fibrotic processes.

The partnership between the UMCG and Takeda Pharmaceuticals aims to develop laboratory methods the study the role of these fibroblast subtypes in IBD development and their applicability as novel therapeutic targets. While we are able to culture fibroblasts from inflamed and fibrotic intestinal tissue of Crohn’s disease patients, the first and most important thing we need to know is how similar or dissimilar the cultured fibroblasts are when compared to the fibroblasts in the original patient tissue. Recent developments in single cell RNA sequencing (scRNAseq) now allows us to make this comparison.

In preparation of this project, we have performed scRNAseq of fibroblasts inflamed and fibrotic tissue of CD patients, where we also cultured fibroblasts from the same tissue. In the PPP project we will perform scRNAseq on the cultured fibroblasts and establish how similar or dissimilar they are from the ones in the original tissue. The results from this project will reveal how suitable the cultured fibroblast are for analyzing novel disease mechanisms of CD and their applicability for developing innovative therapies for CD.