Homeostatic mini-intestines through scaffold-guided organoid morphogenesis

Homeostatic mini-intestines through scaffold-guided organoid morphogenesis

  通过支架引导产生类器官形态发生,实现迷你小肠的构建。

Introduction

  作者假设,将囊性肠类器官塑造成其特有的隐窝和绒毛结构的形态发生过程,可以被利用来促进体外干细胞沿着预定义的空间边界形成,特别是那些近似于肠表面三维拓扑结构的细胞。为此作者创造了一个可以透过气体、营养和大分子的支架,该支架能够促进肠干细胞(intestinal stem cells, ISCs)的有效粘附、增殖和分化,也足够坚硬以作为物理屏障约束ISCs生长成预定义的形状。

  由于纯基质胶(Matrigel)太软而不能限制鼠ISCs生长,作者发现由可提供相对坚硬的、可粘附的基底的I型胶原(type-I collagen)和包含天然基底膜的关键成分的基质胶的混合基质满足所需要求。

LGR5为小肠和结肠干细胞的标记物。

Fig. 1 | Establishment of long-term homeostatic culture of tubular mini-guts

Fig. 2 | Cell-fate patterning and cellular diversity of tubular mini-guts

Fig. 3 | Perspectives for modelling intestine biology and disease

Methods

Microdevice design and fabrication

  参考图1和上图。芯片由三个主要部分组成:

  • 1个中央的水凝胶室用于类器官培养。
  • 水凝胶室侧面的2个基侧培养基贮液槽。
  • 用于微通道灌注的出入口培养基储液槽。

基侧:靠近管壁那面。

Reference

Nikolaev M, Mitrofanova O, Broguiere N, et al. Homeostatic mini-intestines through scaffold-guided organoid morphogenesis[J]. Nature, 2020, 585(7826): 574–578.

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