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Homeostatic mini-intestines through scaffold-guided organoid morphogenesis

机译：稳态迷你肠通过脚手架引导有机体形态发生

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摘要

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.
机译：上皮有机体，例如衍生自肠的干细胞，具有巨大的建模组织和疾病生物学（1-4）。然而，目前使用的方法在三维矩阵（5,6）中导致这些有机体（5,6）导致随机发展组织，其具有限制寿命和尺寸的封闭式囊性结构，限制实验操作并禁止稳态。这里，通过使用组织工程和细胞的内在自组织性质，我们诱导肠道干细胞形成具有可触及的腔的管状上皮细胞和绒毛和绒毛样域的类似空间排列到体内。当连接到外部泵送系统时，迷你齿轮管是灌注的;这允许连续去除死细胞在几周内延长组织寿命，并且还使管与微生物进行殖民，以用于建模宿主微生物相互作用。迷你肠包括常规有机体中很少发现的稀有，专门的细胞类型。他们保留了肠的关键生理标志，并具有显着的再生能力。我们为外部引导干细胞的自组织成功能有机体组织的概念是广义适用的，并且将能够实现更生理的有关的有机体形状，尺寸和功能。

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  • 来源
    《Nature》 |2020年第7826期|574-578|共5页
  • 作者

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

  • 作者单位

    Ecole Polytech Fed Lausanne EPFL Sch Life Sci SV Inst Bioengn Lab Stem Cell Bioengn Lausanne Switzerland;

    Ecole Polytech Fed Lausanne EPFL Sch Life Sci SV Inst Bioengn Lab Stem Cell Bioengn Lausanne Switzerland;

    Ecole Polytech Fed Lausanne EPFL Sch Life Sci SV Inst Bioengn Lab Stem Cell Bioengn Lausanne Switzerland;

    Ecole Polytech Fed Lausanne EPFL Sch Life Sci SV Inst Bioengn Lab Stem Cell Bioengn Lausanne Switzerland;

    Ecole Polytech Fed Lausanne EPFL Sch Life Sci SV Inst Bioengn Lab Stem Cell Bioengn Lausanne Switzerland;

    Ecole Polytech Fed Lausanne EPFL Sch Life Sci SV Inst Bioengn Lab Stem Cell Bioengn Lausanne Switzerland;

    Ecole Polytech Fed Lausanne EPFL Sch Life Sci SV Inst Bioengn Lab Stem Cell Bioengn Lausanne Switzerland;

    Ecole Polytech Fed Lausanne EPFL Sch Life Sci SV Inst Bioengn Lab Stem Cell Bioengn Lausanne Switzerland|Startlab SUN Biosci Epalignes Switzerland;

    Univ Lausanne Electron Microscopy Facil Fac Biol & Med Lausanne Switzerland;

    Ecole Polytech Fed Lausanne EPFL Sch Life Sci SV Inst Bioengn Lab Stem Cell Bioengn Lausanne Switzerland|Roche Pharma Res & Early Dev Basel Switzerland;

    Royal Netherlands Acad Arts & Sci Hubrecht Inst Oncode Inst Utrecht Netherlands|Univ Med Ctr Utrecht Netherlands;

    Ecole Polytech Fed Lausanne EPFL Sch Life Sci SV Inst Bioengn Lab Stem Cell Bioengn Lausanne Switzerland|Ecole Polytech Fed Lausanne Sch Basic Sci SB Inst Chem Sci & Engn Lausanne Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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