4.7 Article

Next-Generation Intestinal Toxicity Model of Human Embryonic Stem Cell-Derived Enterocyte-Like Cells

期刊

FRONTIERS IN VETERINARY SCIENCE
卷 8, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fvets.2021.587659

关键词

alternative testing method; embryonic stem cell; enterotoxicity; intestinal toxicity; toxicology

资金

  1. KRIBB Research Initiative Program [KGM472212209710]
  2. Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University
  3. BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University

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This study established hESC-ELCs as an intestinal toxicity model, showing a stronger correlation with the in vivo model compared to immortalized cell lines. This suggests that hESC-ELCs could serve as the next-generation model for intestinal toxicity assessment.
The gastrointestinal tract is the most common exposure route of xenobiotics, and intestinal toxicity can result in systemic toxicity in most cases. It is important to develop intestinal toxicity assays mimicking the human system; thus, stem cells are rapidly being developed as new paradigms of toxicity assessment. In this study, we established human embryonic stem cell (hESC)-derived enterocyte-like cells (ELCs) and compared them to existing in vivo and in vitro models. We found that hESC-ELCs and the in vivo model showed transcriptomically similar expression patterns of a total of 10,020 genes than the commercialized cell lines. Besides, we treated the hESC-ELCs, in vivo rats, Caco-2 cells, and Hutu-80 cells with quarter log units of lethal dose 50 or lethal concentration 50 of eight drugs-chloramphenicol, cycloheximide, cytarabine, diclofenac, fluorouracil, indomethacin, methotrexate, and oxytetracycline-and then subsequently analyzed the biomolecular markers and morphological changes. While the four models showed similar tendencies in general toxicological reaction, hESC-ELCs showed a stronger correlation with the in vivo model than the immortalized cell lines. These results indicate that hESC-ELCs can serve as a next-generation intestinal toxicity model.

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