Abstract
One of the challenges in predicting human intestinal absorption of drugs is that existing experimental systems have shown poor predictability especially for drugs whose intestinal absorption is dynamically regulated by metabolic enzymes and transporters. We have shown that human crypt-derived intestinal stem cells can undergo continuous expansion and form monolayers of differentiated absorptive epithelial cells on culture dishes or culture inserts by simply changing culture medium. This experimental system is characterized by the expression of multiple uptake and efflux transporters and metabolic enzymes at levels comparable to those of human intact intestinal tissue. Moreover, our cells can reproduce a pattern of gene expression/function of intestinal epithelial cells at the site of crypt collection. This property enables to utilize for quantitative prediction of human intestinal absorption and risk assessment of drug-induced intestinal toxicity.
