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A group of scientists from Japan have found success in growing small intestinal cells, akin to those found in the human body, from human-induced pluripotent stem cells. They assert that the grown cells may be used for laboratory studies focusing on human small intestinal drug metabolism and transport.
Because of this, studies on the absorption of novel oral drugs rely on in vitro or animal models to accurately recreate the environment of the small intestine.
Presently, scientists widely use the human colon cancer cell line Caco-2 as a version of the intestinal epithelium. However, this has its drawbacks: Caco-2 cells are derived from the colon; thus, they more closely resemble the colon compared to the small intestine. By way of instance, these cells do not express cytochrome P450 3A4 (CYP3A4), a protein critical for drug metabolism that’s abundantly expressed in the small intestine. Moreover, Caco-2 cells tend to show high cell-line into cell-line variations.
To tackle these problems, scientists from the Tokyo Institute of Technology, The University of Tokyo, Kanto Chemical Co.. Inc., Shionogi & Co., Ltd. and Shionogi TechnoAdvance Research Co., Ltd., developed publication enterocyte-like cells from human-induced pluripotent stem cells (hiPSCs), which can differentiate into any kind of cell when supplied with right growth factors.
By changing a procedure that they used on human embryonic stem cells, the scientists initially grew cells which resemble the early stages of small intestine cells, called intestinal progenitor cells.
We established an efficient culture procedure for generating enterocyte-like cells from hiPSCs by culturing the hiPSC-derived endoderm or intestine progenitor cells on CVM.”
Dr. Nobuaki Shiraki, Corresponding Author, Associate Professor, Tokyo Institute of Technology
Their efforts resulted in the development of enterocyte-like cells which closely resembled real enterocytes, expressing efflux transporter proteins regulating drug absorption as well as CYP3A4, which Caco-2 cells deficiency.
The scientists assert that these first-of-their-kind enterocyte-like cells can be utilised as an in vitro model of the small intestine for assessing the intestinal absorption of drugs in humans.
Elaborating on the benefits of using these cells for future studies, Dr. Shoen Kume, Professor at Tokyo Institute of Technology, and co-corresponding author of the study, remarks,”The hiPSC-derived enterocyte-like cells established in this research may be used for the quantitative forecast of the intestinal absorption of drugs in humans under specific occasions such as alteration of the functions of transporters/metabolic enzymes by drug-drug interactions as well as normal conditions.”
Indeed, let us hope that the hiPSC-derived enterocyte-like cells would aid breakthrough study in future pharmacokinetic research!
Tokyo Institute of Technology
Yoshida, S., et al. (2021) Generation of human-induced pluripotent stem cell-derived functional enterocyte-like cells for pharmacokinetic studies. Stem Cell Reports. doi.org/10.1016/j.stemcr.2020.12.017.