Construction of small intestine-like tissue by reproducing interstitial flow on-chip

Significant progress has been recently achieved in generating in vitro human small intestine models. Nonetheless, there remains ample opportunity for enhancement, both in terms of structure and function, within the current model. In this study, our objective is to construct a multilayered small intestinal tissue composed of an intestinal epithelium, supportive mesenchymal cells, and an extracellular matrix. We developed a multilayered small intestinal tissue by differentiating human induced pluripotent stem cells on a microfluidic device capable of replicating interstitial flow. Under the interstitial flow exposure, a three-dimensional villus-like epithelium and mature intestinal epithelial cells, including polarized enterocytes or goblet cells, were observed in the small intestine tissue-on-a-chips. Further analysis revealed that intestinal fibroblasts and collagen fiber are localized to the basolateral side of the intestinal epithelium. Moreover, we confirmed that small intestine tissue-on-a-chips are useful for pharmaceutical and infectious disease research. Our small intestine tissue-on-a-chips not only overcome the limitations of conventional small intestine models but also offer a unique opportunity to understand the mechanisms underlying intestinal tissue development.