한빛사논문
Ohman Kwon 1, Hana Lee 1, Jaeeun Jung 1, Ye Seul Son 1, Sojeong Jeon 1, Won Dong Yoo 1 2, Naeun Son 1 2, Kwang Bo Jung 1, Eunho Choi 1 2, In-Chul Lee 3 4, Hyung-Jun Kwon 3 4, Chuna Kim 1 2 5, Mi-Ok Lee 1 2, Hyun-Soo Cho 1 2 6, Dae Soo Kim 1 2, Mi-Young Son 7 8 9 *
1Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
2KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, 34113, Republic of Korea.
3Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, 56212, Republic of Korea.
4KRIBB, Korea Preclinical Evaluation Center, Jeongeup, 56212, Republic of Korea.
5KRIBB, Aging Convergence Research Center, Daejeon, 34141, Republic of Korea.
6Department of Biological Science, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
7Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
8KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, 34113, Republic of Korea.
9Department of Biological Science, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
*Corresponding author: correspondence to Mi-Young Son
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.
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