Controlled aggregative assembly to form self-organizing macroscopic human intestine from induced pluripotent stem cells.

Autor:	Takahashi J; Department of Gastroenterology and Hepatology, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan., Sugihara HY; Department of Gastroenterology and Hepatology, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan., Kato S; Department of Gastroenterology and Hepatology, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan., Kawasaki S; Department of Gastroenterology and Hepatology, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan., Nagata S; Department of Gastroenterology and Hepatology, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan., Okamoto R; Department of Gastroenterology and Hepatology, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan., Mizutani T; Department of Gastroenterology and Hepatology, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: tmizutani.gast@tmd.ac.jp.
Jazyk:	angličtina
Zdroj:	Cell reports methods [Cell Rep Methods] 2024 Dec 16; Vol. 4 (12), pp. 100930. Date of Electronic Publication: 2024 Dec 10.
DOI:	10.1016/j.crmeth.2024.100930
Abstrakt:	Human intestinal organoids (HIOs) derived from human pluripotent stem cells (hPSCs) are promising resources for intestinal regenerative therapy as they recapitulate both endodermal and mesodermal components of the intestine. However, due to their hPSC-line-dependent mesenchymal development and spherical morphology, HIOs have limited applicability beyond basic research and development. Here, we demonstrate the incorporation of separately differentiated mesodermal and mid/hindgut cells into assembled spheroids to stabilize mesenchymal growth in HIOs. In parallel, we generate tubular intestinal constructs (assembled human intestinal tubules [a-HITs]) by leveraging the high aggregative property of assembled spheroids. Through rotational culture in a bioreactor, a-HITs self-organize to develop epithelium and supportive mesenchyme. Upon mesenteric transplantation, a-HITs mature into centimeter-scale tubular intestinal tissue with complex architectures. Our aggregation- and suspension-based approach offers basic technology for engineering tubular intestinal tissue from hPSCs, which could be ultimately applied to the generation of the human intestine for clinical application. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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