EP4117718A1 — Inflammatory bowel disease stem cells, agents which target ibd stem cells, and uses related thereto

USPTO Abstract

The present disclosure addresses IBD from the standpoint of inhibiting or ablating pathogenic mucosal stem cells cloned from defined regions of disease in the gastrointestinal tract. In the case of Crohn's disease, for example, isolation of those stem cells according to the methods of the present disclosure reveals a pattern of inflammatory gene expression in stem cells from the terminal ileum and colon that is epigenetically maintained despite months of continuous cultivation in the absence of immune or stromal cells, or of intestinal microbes. Superimposed on this distributed inflammatory phenotype is a differentiation defect that profoundly and specifically alters the mucosal barrier properties of the terminal ileum. The co-existence of diseased and normal stem cells within the same endoscopic biopsies of Crohn's disease patients implicates an epigenetically enforced heterogeneity among mucosal stem cells in the dynamics of this condition.