The small intestine is critical tissue involving in pharmacokinetics of oral drugs. Human primary enterocytes are expected to provide the closest in vitro model to human intestine. However, it is difficult to obtain these cells for use in pharmacokinetic study. Human colon adenocarcinoma cell line Caco-2 are frequently used for a prediction of drug absorption in the small intestine. However, in Caco-2 cells, the expression levels of transporters and drug metabolizing enzymes are different from human intestine. The utilization of human induced pluripotent stem cells (hiPSCs) is expected for a variety of applications involving the drug development studies such as prediction of drug metabolism and toxicity of drug candidates. We have developed the differentiation methods of hiPSCs into pharmacokinetically functional small intestinal epithelial cells using small molecular compounds that activate cAMP signaling during the intestinal differentiation.
Microphysiological system (MPS), that mimics the human body and connects several tissues or organs with microfluidic system, has been recently developed, and utilization of the chip in the drug development is attracted attention as advanced research field of human in vitro models.
We are attempting to develop a device that can predict the pharmacokinetics and toxicicity in vitro. We are expecting that hiPSC-derived cells and MPS will be used in drug evaluation systems.