Mechanically induced development and maturation of human intestinal organoids in vivo.

Mechanically induced development and maturation of human intestinal organoids in vivo.
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DOI:
10.1038/s41551-018-0243-9
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发表时间:
2018-06
影响因子:
28.1
通讯作者:
Mahe MM
Mahe MM
中科院分区:
工程技术1区
文献类型:
--
作者:
Poling HM;Wu D;Brown N;Baker M;Hausfeld TA;Huynh N;Chaffron S;Dunn JCY;Hogan SP;Wells JM;Helmrath MA;Mahe MM

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干细胞自组织成功能性组织的天然能力已被用于生产功能性人类肠道器官。虽然动态机械力在肠道发育和形态发生中起着核心作用,但传统的肠道类器官生成方法仅依赖于生物因素。在这里,我们表明,通过使用压缩的镍钛合金弹簧,将单轴菌株掺入移植到小鼠肠系膜的人肠道器官中,可以诱导器官的生长和成熟。对暴露于菌株的组织的形态参数、转录组图谱和功能分析的评估显示,在组织大小和复杂性以及肌肉张力方面,与天然人类肠道有更高的相似性。我们的发现表明,在人类肠道组织的发育过程中,加入与生理相关的机械线索可以促进其成熟和肠道发生。
The natural ability of stem cells to self-organize into functional tissue has been harnessed for the production of functional human intestinal organoids. Although dynamic mechanical forces play a central role in intestinal development and morphogenesis, conventional methods for the generation of intestinal organoids have relied solely on biological factors. Here, we show that the incorporation of uniaxial strain, by using compressed nitinol springs, in human intestinal organoids transplanted into the mesentery of mice induces growth and maturation of the organoids. Assessment of morphometric parameters, transcriptome profiling, and functional assays of the strain-exposed tissue revealed higher similarities to native human intestine, with regards to tissue size and complexity, and muscle tone. Our findings suggest that the incorporation of physiologically relevant mechanical cues during the development of human intestinal tissue enhances its maturation and enterogenesis.
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