{Reference Type}: Journal Article
{Title}: Construction of multilayered small intestine-like tissue by reproducing interstitial flow.
{Author}: Deguchi S;Kosugi K;Takeishi N;Watanabe Y;Morimoto S;Negoro R;Yokoi F;Futatsusako H;Nakajima-Koyama M;Iwasaki M;Yamamoto T;Kawaguchi Y;Torisawa YS;Takayama K;
{Journal}: Cell Stem Cell
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 3
{Factor}: 25.269
{DOI}: 10.1016/j.stem.2024.06.012
{Abstract}: 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.