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

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.
Competing Interests: Declaration of interests K.T. and S.D. are inventors on JP patent application no. 2023-132372 “Construction of micro-small intestine systems”. K.T. receives research funds for developing micro-small intestine systems under the contract with Kanto Chemical Co., Inc. M.I. is a scientific adviser for xFOREST Therapeutics without salary.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)