Chemically-defined and scalable culture system for intestinal stem cells derived from human intestinal organoids

Ohman Kwon, Hana Lee, Jaeeun Jung, Ye Seul Son, Sojeong Jeon, Won Dong Yoo, Naeun Son, Kwang Bo Jung, Eunho Choi, In-Chul Lee, Hyung-Jun Kwon, Chuna Kim, Mi-Ok Lee, Hyun-Soo Cho, Dae Soo Kim and Mi-Young Son ()
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Ohman Kwon: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Hana Lee: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Jaeeun Jung: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Ye Seul Son: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Sojeong Jeon: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Won Dong Yoo: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Naeun Son: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Kwang Bo Jung: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Eunho Choi: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
In-Chul Lee: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Hyung-Jun Kwon: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Chuna Kim: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Mi-Ok Lee: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Hyun-Soo Cho: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Dae Soo Kim: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Mi-Young Son: Korea Research Institute of Bioscience and Biotechnology (KRIBB)

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-45103-7

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