日本庆应义塾大学医学院Toshiro Sato、Eiji Kobayashi研究小组，利用基于类器官的器官重建方法治疗短肠综合征（SBS）。相关论文于2021年2月25日发表于《自然》杂志。
研究人员利用回肠衍生的类器官替代天然结肠上皮细胞，从而生成了功能性小肠结肠（SIC）。研究人员首先发现异种移植的人回肠类器官保持了其区域身份并可在小鼠结肠中形成新生的绒毛结构。类器官单层细胞体外培养实验进一步揭示了腔内机械流在绒毛形成中的重要作用。
随后，研究人员通过将SIC重新定位在回盲肠交界处来生成大鼠SIC模型，在回盲交界处上皮暴露于恒定的管腔肠液流。这种解剖学上的重定位为SIC提供了小肠的器官结构，包括完整的脉管和神经支、绒毛结构和乳腺（小肠特有脂肪吸收淋巴结构）。SIC具有吸收功能，在SBS大鼠模型中可显著改善肠道衰竭，移植结肠类器官而非回肠类器官将导致个体死亡。这些数据为肠类器官应用于再生提供了原理证明，并为SBS治疗提供了可行的策略。
据了解，小肠是吸收营养的主要器官，其大量切除会导致吸收不良和消瘦，这被称为短肠综合症。类器官技术可以在体外有效地扩展肠道上皮组织，但是对于重建整个小肠（包括复杂的淋巴血管系统）仍存在困难。
附：英文原文
Title: An organoid-based organ-repurposing approach to treat short bowel syndrome
Author: Shinya Sugimoto, Eiji Kobayashi, Masayuki Fujii, Yuki Ohta, Kazuya Arai, Mami Matano, Keiko Ishikawa, Kentaro Miyamoto, Kohta Toshimitsu, Sirirat Takahashi, Kosaku Nanki, Yoji Hakamata, Takanori Kanai, Toshiro Sato
Issue&Volume: 2021-02-24
Abstract: The small intestine is the main organ for nutrient absorption, and its extensive resection leads to malabsorption and wasting conditions referred to as short bowel syndrome (SBS). Organoid technology enables an efficient expansion of intestinal epithelium tissue in vitro1, but reconstruction of the whole small intestine, including the complex lymphovascular system, has remained challenging2. Here we generate a functional small intestinalized colon (SIC) by replacing the native colonic epithelium with ileum-derived organoids. We first find that xenotransplanted human ileum organoids maintain their regional identity and form nascent villus structures in the mouse colon. In vitro culture of an organoid monolayer further reveals an essential role for luminal mechanistic flow in the formation of villi. We then develop a rat SIC model by repositioning the SIC at the ileocaecal junction, where the epithelium is exposed to a constant luminal stream of intestinal juice. This anatomical relocation provides the SIC with organ structures of the small intestine, including intact vasculature and innervation, villous structures, and the lacteal (a fat-absorbing lymphatic structure specific to the small intestine). The SIC has absorptive functions and markedly ameliorates intestinal failure in a rat model of SBS, whereas transplantation of colon organoids instead of ileum organoids invariably leads to mortality. These data provide a proof of principle for the use of intestinal organoids for regenerative purposes, and offer a feasible strategy for SBS treatment.
DOI: 10.1038/s41586-021-03247-2
Source: https://www.nature.com/articles/s41586-021-03247-2
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
