Nature Communications (Jan 2024)

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,
  • Mi-Young Son

DOI
https://doi.org/10.1038/s41467-024-45103-7
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 14

Abstract

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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.