小柯机器人

科学家利用类器官在体外构建出迷你小肠
2020-09-18 15:23

瑞士洛桑理工学院Matthias P. Lutolf小组通过支架引导的类器官形态发生,实现迷你小肠的构建。相关论文于2020年9月16日在线发表在《自然》杂志上。

通过使用组织工程和细胞的固有自组织特性,研究人员将肠干细胞诱导形成管状上皮,其具有可及的内腔以及与体内类似的隐窝和绒毛状结构域空间分布。当连接到外部抽水系统时,迷你肠腔是可灌洗的。这样可以连续去除死细胞,从而将组织寿命延长数周,还可以使试管中充满微生物,进而模拟宿主与微生物之间的相互作用。
 
迷你肠道包括罕见的特殊细胞类型,这些类型在常规类器官中很少见。它们保留了肠道的关键生理特征,并具有显著的再生能力。这一干细胞自我组织为功能性类器官类的概念是广泛适用的,并且将能够实现更多与生理相关的类器官的形状、大小和功能。
 
据悉,上皮类器官,例如从肠干细胞衍生的类器官,在建模组织和疾病生物学方面具有巨大的潜力。但是,目前在三维基质中产生这些类器官的方法导致了具有封闭囊状结构的随机发育组织,这些结构限制了其寿命和大小,从而??限制了实验操作并无法实现内稳态。
 
附:英文原文

Title: Homeostatic mini-intestines through scaffold-guided organoid morphogenesis

Author: Mikhail Nikolaev, Olga Mitrofanova, Nicolas Broguiere, Sara Geraldo, Devanjali Dutta, Yoji Tabata, Bilge Elci, Nathalie Brandenberg, Irina Kolotuev, Nikolce Gjorevski, Hans Clevers, Matthias P. Lutolf

Issue&Volume: 2020-09-16

Abstract: Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology1,2,3,4. However, the approaches that are used at present to derive these organoids in three-dimensional matrices5,6 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.

DOI: 10.1038/s41586-020-2724-8

Source: https://www.nature.com/articles/s41586-020-2724-8

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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

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