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- Title
Chemically-defined and scalable culture system for intestinal stem cells derived from human intestinal organoids.
- Authors
Kwon, Ohman; Lee, Hana; Jung, Jaeeun; Son, Ye Seul; Jeon, Sojeong; Yoo, Won Dong; Son, Naeun; Jung, Kwang Bo; Choi, Eunho; Lee, In-Chul; Kwon, Hyung-Jun; Kim, Chuna; Lee, Mi-Ok; Cho, Hyun-Soo; Kim, Dae Soo; Son, Mi-Young
- Abstract
Three-dimensional human intestinal organoids (hIO) are widely used as a platform for biological and biomedical research. However, reproducibility and challenges for large-scale expansion limit their applicability. Here, we establish a human intestinal stem cell (ISC) culture method expanded under feeder-free and fully defined conditions through selective enrichment of ISC populations (ISC3D-hIO) within hIO derived from human pluripotent stem cells. The intrinsic self-organisation property of ISC3D-hIO, combined with air-liquid interface culture in a minimally defined medium, forces ISC3D-hIO to differentiate into the intestinal epithelium with cellular diversity, villus-like structure, and barrier integrity. Notably, ISC3D-hIO is an ideal cell source for gene editing to study ISC biology and transplantation for intestinal diseases. We demonstrate the intestinal epithelium differentiated from ISC3D-hIO as a model system to study severe acute respiratory syndrome coronavirus 2 viral infection. ISC3D-hIO culture technology provides a biological tool for use in regenerative medicine and disease modelling. Challenges in reproducibility and large-scale expansion limit the current applicability of human intestinal organoids. Here, the authors present a feeder-free, chemically-defined culture method for enrichment of intestinal stem cells isolated from 3D human intestinal organoids.
- Subjects
STEM cells; PLURIPOTENT stem cells; HUMAN stem cells; CELL culture
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-45103-7