Organoids as regenerative medicine for inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a chronic disorder with an increasing global prevalence. Managing disease activity relies on various pharmacological options. However, the effectiveness of current therapeutics is limited and not universally applicable to all patients and circumstances. Consequently, developing new management strategies is necessary. Recent advances in endoscopically obtained intestinal biopsy specimens have highlighted the potential of intestinal epithelial organoid transplantation as a novel therapeutic approach. Experimental studies using murine and human organoid transplantations have shown promising outcomes, including tissue regeneration and functional recovery. Human trials with organoid therapy have commenced; thus, this article provides readers with insights into the necessity and potential of intestinal organoid transplantation as a new regenerative therapeutic option in clinical settings and explores its associated challenges.

Keywords: Cell biology; Immunology; Molecular biology; Stem cells research.

Graphical abstract

Figure 1

Colonic barrier Under normal circumstances, the colonic epithelial barrier provides protection against pathogens (diet and microbiome) of the intestinal lumen. The cells of the healthy epithelial barrier are continuously replenished by intestinal stem cell differentiation and proliferation. However, during inflammation, the intestinal stem cells may be broken down. Thus, chronic inflammation may result in the depletion of intestinal stem cells and an inability to replace the epithelial cells and maintain the colonic barrier. Breakdown of the intestinal barrier (i.e., “leaky gut”) is involved in several intestinal conditions, including UC and CD. Engraftment of intestinal organoids will, in addition to provide new intestinal stem cells, restore the barrier function and resolve the chronic inflammation.

Figure 2

Phases of intestinal organoids as regenerative therapy Using a colonoscope, biopsy specimens are acquired from healthy sections of the colonic epithelium. From these specimens, intestinal stem cell-containing crypts are isolated and cultured in vitro. After organoid formation and subsequent expansion, organoids are transplanted back to the diseased intestinal areas to repair and regenerate the damaged epithelium.

Figure 3

Proposed phases of construction of a small intestinalized colon Intestinal organoids are developed from biopsies of the ileum. These organoids will develop ileal epithelium and preserve ileal characteristics following engraftment in a section of the colon, where the colonic epithelium has been removed. This will result in a section of the colon with ileal epithelium (i.e., a small intestinalized colon (SIC)). Subsequently, the SIC is surgically translocated to the ileum to enable the complete formation of villi and lacteals, thus promoting the absorption of nutrients.