Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology 1 – 4 . However, the approaches that are used at present to derive these organoids in three-dimensional matrices 5 , 6 result in stochastically developing tissues with a closed, cystic architecture that restricts lifespan and size, limits experimental manipulation and prohibits homeostasis. Here, by using tissue engineering and the intrinsic self-organization properties of cells, we induce intestinal stem cells to form tube-shaped epithelia with an accessible lumen and a similar spatial arrangement of crypt- and villus-like domains to that in vivo. When connected to an external pumping system, the mini-gut tubes are perfusable; this allows the continuous removal of dead cells to prolong tissue lifespan by several weeks, and also enables the tubes to be colonized with microorganisms for modelling host–microorganism interactions. The mini-intestines include rare, specialized cell types that are seldom found in conventional organoids. They retain key physiological hallmarks of the intestine and have a notable capacity to regenerate. Our concept for extrinsically guiding the self-organization of stem cells into functional organoids-on-a-chip is broadly applicable and will enable the attainment of more physiologically relevant organoid shapes, sizes and functions. Miniature gut tubes grown in vitro from mouse intestinal stem cells are perfusable, can be colonized with microorganisms and exhibit a similar arrangement and diversity of specialized cell types to intestines in vivo.

中文翻译：

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通过支架引导的类器官形态发生实现稳态小肠

上皮类器官，例如源自肠道干细胞的类器官，在组织和疾病生物学建模方面具有巨大潜力 1-4。然而，目前用于在三维矩阵 5 、 6 中导出这些类器官的方法会导致随机发育的组织具有封闭的囊状结构，从而限制寿命和大小、限制实验操作并禁止体内平衡。在这里，通过使用组织工程和细胞的内在自组织特性，我们诱导肠道干细胞形成管状上皮，具有可接近的管腔和与体内类似的隐窝和绒毛样结构域的空间排列。当连接到外部泵系统时，迷你肠管是可灌注的；这允许持续去除死细胞以将组织寿命延长数周，并且还使管能够被微生物定植以模拟宿主-微生物相互作用。小肠包括罕见的、特化的细胞类型，在传统的类器官中很少发现。它们保留了肠道的关键生理特征，并具有显着的再生能力。我们从外在引导干细胞自组织成为功能性类器官芯片的概念具有广泛的适用性，并将能够实现更多生理相关的类器官形状、大小和功能。从小鼠肠道干细胞体外培养的微型肠管是可灌注的，