Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies

Abstract

SummaryThe small intestine plays an important role in the absorption and metabolism of oral drugs. In the current evaluation system, it is difficult to predict the precise absorption and metabolism of oral drugs. In this study, we generated small intestinal epithelial-like cells from human induced pluripotent stem cells (hiPS-SIECs), which could be applied to drug absorption and metabolism studies. The small intestinal epithelial-like cells were efficiently generated from human induced pluripotent stem cell by treatment with WNT3A, R-spondin 3, Noggin, EGF, IGF-1, SB202190, and dexamethasone. The gene expression levels of small intestinal epithelial cell (SIEC) markers were similar between the hiPS-SIECs and human adult small intestine. Importantly, the gene expression levels of colonic epithelial cell markers in the hiPS-SIECs were much lower than those in human adult colon. The hiPS-SIECs generated by our protocol exerted various SIEC functions. In conclusion, the hiPS-SIECs can be utilized for evaluation of drug absorption and metabolism.

Establishment of a novel culture method for maintaining intestinal stem cells derived from human induced pluripotent stem cells

“…As a result, evaluation of intestinal pharmacokinetics is very important. Several studies have been undertaken with a focus on differentiating human iPS cells into intestinal cells (Negoro et al, 2018;Zhang et al, 2018;Ozawa et al, 2015;Ogaki et al, 2015), and the uses of intestinal cells have received increasing attention. We previously reported the usefulness of intestinal enterocytes derived from human iPS cells (Kabeya et al, 2018;Kodama et al, 2016;Iwao et al, 2015Iwao et al, , 2014.…”

Photoactivatable oncolytic adenovirus for optogenetic cancer therapy

“…Human small intestinal organoids (SIO) were generated from human iPS cells using a STEMdiff intestinal organoid kit (STEMCELL Technologies). The method for culturing human iPS cells was performed according to our previous reports 6,7 .…”

“…5 Division of Materials Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma 630-0192, Japan. 6 Global Center for Medical Engineering and Informatics, Osaka University, Osaka 565-0871, Japan. 7 Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka 565-0871, Japan…”

Restoring aged stem cell functionality: Current progress and future directions

“…However, high-functioning iPSC-derived NSCs, SSCs, ISCs, and MuSCs have been successfully made and used in non-agingfocused studies, suggesting this may be a potential avenue of restoration for multiple types of stem cells. [56][57][58][59] Rather than isolating and implanting rejuvenated stem cells, reprogramming at the organismal level aimed to directly produce the same benefits in vivo. However, while pulsing of reprogramming factors has been shown to generate short-term beneficial effects, long-term expression of these factors causes teratoma formation.…”