Human intestinal organoids as a valuable tool to investigate human intestinal biology.

Abstract

Intestinal organoids have been regarded as valuable tools for investigating the physiological functions of the human intestinal epithelium, including nutrient absorption and xenobiotic metabolism. However, owing to the high culture cost and handling complexity, their use is not as widespread as expected in both academia and industry. To overcome this issue, we developed multiple fundamental methodologies for the routine use of human organoids with minimal differences among users. Based on these results, human intestinal organoids can now be cultured on a large scale at a significantly lower cost, which enables compound screening, including screening of drug candidates that exhibit cytotoxicity, which may lead to intestinal toxicity. We also demonstrated that human intestinal organoids can reproduce physiological functions and phenomena in the human intestinal epithelium, which are difficult to evaluate in some experimental animals and cancer-derived human cell lines, and are expected to provide impetus to accelerate organoid research.