Abstract
[Purpose]
Currently, cultured cells such as Caco-2 cells and experimental animals are used as a model system of the human small intestine. However, these model systems show poor correlation with human small intestine. In this investigation, we generated human iPS cell-derived small intestinal epithelial like cells and attempted to develop an in vitro model that has properties closer to those of the human small intestine than existing models.
[Method]
We established a method for inducing differentiation of human iPS cells into intestinal epithelial cells based on a previous report (Kabeya, et al. Drug Metab. Pharmacokinet. 2020) and developed cryopreserved human iPS cell-derived intestinal epithelial cells (F-hiSIECTM). In addition to characterizing these cells, we constructed various intestinal evaluation models.
[Result]
The mRNA expression of intestinal epithelial cell markers, transporters, and metabolic enzymes was similar to that in the adult small intestine. In addition, stable transporter activity and metabolic enzyme activity were exhibited among multiple lots differentiated from iPS cells, and it was possible to evaluate the intestinal absorption of compounds by using these cells. Furthermore, it was shown that inflammatory reactions, pharmacokinetics, and toxic reactions could be predicted in various intestinal tract models constructed using these cells. These results suggest that F-hiSIECTM may be useful for in vitro evaluation of the function of the human small intestine.
