Nature子刊:机械力促进肠道类器官的发育成熟

动态机械力在肠道发育及形态发生中起到重要作用,但传统的肠道类器官产生方法中大多仅考虑了生物因素;
在移植进小鼠肠系膜的人体肠道类器官中,利用压缩镍钛诺弹簧引入单轴向应变,可促进类器官的生长及成熟;
形成的类器官在组织大小、复杂性、肌张力、形态计量参数、转录谱、功能等方面,均与天然的人体肠道相似;
生理相关的机械力在人体肠道发育过程中促进了肠道发生及肠道成熟。
延伸阅读

Mechanically induced development and maturation of human intestinal organoids in vivo

机械力诱导的人体肠道类器官在体内的发育及成熟

2018-06-04, Article, 10.1038/s41551-018-0243-9more

Abstract:
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, 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 regard 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.

First Authors:
Holly M Poling

Correspondence Authors:
Maxime M Mahe

All Authors:
Holly M Poling,David Wu,Nicole Brown,Michael Baker,Taylor A Hausfeld,Nhan Huynh,Samuel Chaffron,James C Y Dunn,Simon P Hogan,James M Wells,Michael A Helmrath,Maxime M Mahe