日本庆应义塾大学医学院Toshiro Sato课题组宣布他们的研究显示,保留生态位移植促进大鼠短肠综合征肠道类器官的功能植入。相关论文于2025年12月29日发表在《细胞—干细胞》杂志上。
该研究团队展示了一种保留生态位的移植策略,能够高效地将肠道类器官植入大鼠小肠。用N-乙酰半胱氨酸清除腔内粘液有助于乙二胺四乙酸(EDTA)为基础的上皮脱离,使Lgr5+干细胞的去除成为可能,同时保留基质生态位。这种预处理增加了移植物面积,并使回肠产生,从而改善了大鼠SBS的体重轨迹和存活率。
此外,移植的上皮赋予了空肠胆汁酸吸收能力。这些发现为干细胞生态位理论提供了活体证据,表明生态位对于容纳供体干细胞是必不可少的,并建立回化空肠作为自体干细胞的途径,区域靶向治疗SBS。
据了解,短肠综合征(SBS)是一种危及生命的疾病,其预后往往严重依赖于回肠功能,回肠功能是唯一专门用于胆汁酸摄取和有效脂肪吸收的肠段。然而,恢复回肠上皮特异性营养吸收是否能改善SBS仍不清楚。
附:英文原文
Title: Niche-preserving transplantation promotes functional engraftment of intestinal organoids in rat short bowel syndrome
Author: 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
Issue&Volume: 2025-12-29
Abstract: 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.
DOI: 10.1016/j.stem.2025.12.007
Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00441-2
Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:25.269
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx
