%0 Journal Article
%T Construction of multilayered small intestine-like tissue by reproducing interstitial flow.
%A Deguchi S
%A Kosugi K
%A Takeishi N
%A Watanabe Y
%A Morimoto S
%A Negoro R
%A Yokoi F
%A Futatsusako H
%A Nakajima-Koyama M
%A Iwasaki M
%A Yamamoto T
%A Kawaguchi Y
%A Torisawa YS
%A Takayama K
%J Cell Stem Cell
%V 0
%N 0
%D 2024 Jul 3
%M 38996472
%F 25.269
%R 10.1016/j.stem.2024.06.012
%X 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.