Vital functions of the intestines: digestion, absorption, and surface barrier are performed by the intestinal epithelium, which consists of various differentiated cells and intestinal stem cells. Recent technological advances in sequencing technology, including single-cell transcriptomics and epigenetic analysis, have facilitated the genetic characterization of diverse intestinal epithelial cell types and surrounding mesenchymal niche environments. Organoids have allowed biological analysis of the human intestinal epithelium in coordination with genome engineering, genetic lineage tracing, and transplantation into orthotopic tissue. Together, these technologies have prompted the development of organoid-based regenerative therapies for intestinal diseases, including short-bowel syndrome. This article provides an overview of the current understanding of intestinal epithelial self-renewal during homeostasis and regeneration and provides a perspective for future organoid medicine.

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The potential of adult-derived intestinal epithelium to reconstruct intestinal tissue: organoid cultures recapitulate human intestinal stem cell expansion while preserving their original tissue traits, including intestinal region-specific differentiation programs and villus-formation capacity. These traits were well- represented in intracolonic transplantation, where the transplanted small intestinal organoids preserved the original tissue identity and reconstructed the subepithelial colonic tissues toward the small intestine-like crypt–villus structures. This review provides an overview of the potential of the adult intestinal epithelium in establishing and maintaining tissue identity during development and regeneration.

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