オンチップでの小腸上皮-間葉相互作用の再現と創薬研究への応用

抄録

The differentiation and homeostasis of small intestinal epithelium are regulated, with essential support from mesenchymal cells in the lamina propria. However, the existing in vitro small intestine models have limitations because they only consist of epithelial cells and lack mesenchymal cells, which restricts their functionality. Additionally, conventional static cell culture systems do not allow for the exposure of cells to physiological dynamic stimulations. Here, to develop small intestine tissue-on-a-chip, we integrated human iPS cells, capable of differentiating into both small intestinal epithelial and mesenchymal cells simultaneously, with a microfluidic device that mimics the mechanical stimulation in the small intestine. Under fluidic flow exposure, small intestine tissue-on-a-chip developed a 3D crypt-villus axis-like structure and expressed higher levels of mature intestinal markers compared to the static cultured chip, promoting intestinal differentiations. Further analysis revealed the pivotal role of medium flow in orienting intestinal fibroblasts and collagen fibers, contributing to the maturation of intestinal epithelial cells within the small intestine tissue-on-a-chip. Our small intestine tissue-on-a-chip offers a greater level of precision in understanding the pathophysiology of intestinal diseases.