Generation of Budding-Like Intestinal Organoids from Human Induced Pluripotent Stem Cells.

J Pharm Sci

Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan; Educational Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.

Published: July 2021

AI Article Synopsis

  • - Researchers developed new intestinal organoids from human iPS cells that better mimic mature small intestine structures, overcoming issues with previous methods.
  • - These organoids exhibited high levels of key drug transporters and can imitate gut diseases when exposed to specific cytokines, allowing for a better understanding of conditions like mucosal damage and intestinal fibrosis.
  • - The organoids maintained their intestinal properties and showed significant electrical resistance when cultured in a specific setup, indicating their potential for use in disease modeling and drug testing.

Article Abstract

Human induced pluripotent stem (iPS) cell-derived intestinal organoids have low invasiveness; however, the current differentiation method does not reflect the crypt-villus-like structure due to structural immaturity. Here, we generated budding-like organoids that formed epithelial tissue-like structures and had the characteristics of the mature small intestine from human iPS cells. They showed a high expression of drug transporters and induced the expression of cytochrome P450 3A4 and P-glycoprotein. When treated with tumor necrosis factor-α and/or transforming growth factor-β, the budding-like organoids replicated the pathogenesis of mucosal damage or intestinal fibrosis. Upon dissociation and seeding on cell culture inserts, the organoids retained intestinal characteristics, forming polarized intestinal folds with approximately 400 Ω × cm transepithelial electrical resistance. This novel method has great potential for disease modeling and drug screening applications.

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Source
http://dx.doi.org/10.1016/j.xphs.2021.03.014DOI Listing

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