Construction of multilayered small intestine-like tissue by reproducing interstitial flow

• DOI: 10.1016/j.stem.2024.06.012
• Publication Date: 2024-07-11T14:36:37Z
• Authors: Sayaka Deguchi; Kaori Kosugi; Naoki Takeishi; Yukio Watanabe; Shiho Morimoto; Ryosuke Negoro; Fuki Yokoi; Hiroki Futatsusako; May Nakajima-Koyama; Mio Iwasaki; Takuya Yamamoto; Yoshiya Kawaguchi; Yu-suke Torisawa; Kazuo Takayama

Recent advances have made modeling human small intestines in vitro possible, but it remains a challenge to recapitulate fully their structural and functional characteristics. We suspected interstitial flow within the intestine, powered by circulating blood plasma during embryonic organogenesis, to be a vital factor. We aimed to construct an in vivo-like multilayered small intestinal tissue by incorporating interstitial flow into the system and, in turn, developed the micro-small intestine system by differentiating definitive endoderm and mesoderm cells from human pluripotent stem cells simultaneously on a microfluidic device capable of replicating interstitial flow. This approach enhanced cell maturation and led to the development of a three-dimensional small intestine-like tissue with villi-like epithelium and an aligned mesenchymal layer. Our micro-small intestine system not only overcomes the limitations of conventional intestine models but also offers a unique opportunity to gain insights into the detailed mechanisms underlying intestinal tissue development.