Stem Cells. 2022 Mar 4;sxac014. doi: 10.1093/stmcls/sxac014. Online ahead of print.

Theresa Louise Boye ¹, Casper Steenholdt ¹, Kim Bak Jensen ^2 3, Ole Haagen Nielsen ¹

Author information

¹Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.

²Novo Nordisk Foundation Center for Stem Cell Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

³Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.

Abstract

The pathogenesis of inflammatory bowel diseases (IBD) involves genetic predisposition, environmental factors, and a broadly dysregulated intestinal immune response to the commensal intestinal microflora. The interface between genetic predisposition and environmental factors is reflected in the epigenetic regulation at the transcriptional level. Treatment targets now involve mucosal and histological healing, but the future might additionally include normalization of intestinal cellular functions also at the molecular level, for example comprising complete restoration of phenotypic, genotypic, and epigenetic states. Recent developments in patient-derived epithelial intestinal stem cell (ISC) organoid technologies have opened exciting new therapeutic opportunities to potentially attain molecular healing by combining stem cell therapy with molecular manipulations using (epi)drugs and/or CRISPR/Cas9 genome editing. Here, we are the first to discuss the possibility for phenotypic, genotypic, and epigenetic restoration via molecular manipulations and stem cell therapy in IBD from a clinical perspective.