2025-12-30 慶應義塾大学 医学部,東北大学,科学技術振興機構
図 1 研究成果の概略図
<関連情報>
- https://www.jst.go.jp/pr/announce/20251230/index.html
- https://www.jst.go.jp/pr/announce/20251230/pdf/20251230.pdf
- https://www.sciencedirect.com/science/article/pii/S1934590925004412
ニッチ保存移植はラット短腸症候群における腸オルガノイドの機能的生着を促進する Niche-preserving transplantation promotes functional engraftment of intestinal organoids in rat short bowel syndrome
Ryoma Endo, Shinya Sugimoto, Yutaro Kuwashima, Mami Matano, Hikaru Hanyu, Sirirat Takahashi, Hirochika Kato, Taku Tanaka, Andreas Michael Sihombing, Koji Shirosaki, Yoshiko Hatano, Yuki Sugiura, Takanori Kanai, Motoshi Wada, Toshiro Sato
Cell Stem Cell Available online: 29 December 2025
DOI:https://doi.org/10.1016/j.stem.2025.12.007
Highlights
- New passage method enables stable establishment of rat ileal organoids
- Mucin depletion enables niche-preserving, efficient organoid transplantation
- Ilealization of the jejunum ameliorates rat short bowel syndrome
- Ilealization confers bile acid-absorptive capacity to the jejunum
Summary
Short bowel syndrome (SBS) is a life-threatening condition in which outcomes often critically depend on ileal function, the only intestinal segment specialized for bile acid uptake and efficient fat absorption. However, whether restoring ileal epithelium-specific nutrient absorption can ameliorate SBS has remained unknown. Here, we demonstrate a niche-preserving transplantation strategy enabling highly efficient engraftment of intestinal organoids into the rat small intestine. Clearing luminal mucus with N-acetylcysteine facilitates ethylenediaminetetraacetic acid (EDTA)-based epithelial detachment, enabling removal of Lgr5+ stem cells while preserving the stromal niche. This preconditioning increased the engrafted area and enabled the generation of an ilealized jejunum that improved body-weight trajectories and survival in rat SBS. Furthermore, the engrafted epithelia endowed the jejunum with bile acid absorption capacity. These findings provide in vivo evidence for stem cell niche theory, showing that the niche is essential to accommodate donor stem cells, and establish ilealized jejunum as a path toward autologous, region-targeted therapy for SBS.
