研究人员描述了在空间和时间上控制类器官形成的方法，从而使随机的过程更具有确定性。生物工程化的干细胞微环境被用来指定肠道类器官的初始几何形状，这反过来又控制了它们的模式化和隐窝形成。研究人员利用培养的可重复性和可预测性来确定了上皮细胞模式化的基本机制，这可能有助于加强体内的肠道区域化。通过控制类器官培养，研究人员展示了这些结构如何被用来回答标准的、更多变的类器官模型所不能轻易解决的问题。
据了解，上皮类器官是干细胞衍生的组织，接近真实器官的各个方面，因此它们有可能成为基础和转化研究的有力工具。根据定义，它们是自组织的，但形成的结构往往是异质的和不可复制的，这限制了它们在实验室和临床的应用。
附：英文原文
Title: Tissue geometry drives deterministic organoid patterning
Author: N. Gjorevski, M. Nikolaev, T. E. Brown, O. Mitrofanova, N. Brandenberg, F. W. DelRio, F. M. Yavitt, P. Liberali, K. S. Anseth, M. P. Lutolf
Issue&Volume: 2022-01-07
Abstract: Epithelial organoids are stem cell–derived tissues that approximate aspects of real organs, and thus they have potential as powerful tools in basic and translational research. By definition, they self-organize, but the structures formed are often heterogeneous and irreproducible, which limits their use in the lab and clinic. We describe methodologies for spatially and temporally controlling organoid formation, thereby rendering a stochastic process more deterministic. Bioengineered stem cell microenvironments are used to specify the initial geometry of intestinal organoids, which in turn controls their patterning and crypt formation. We leveraged the reproducibility and predictability of the culture to identify the underlying mechanisms of epithelial patterning, which may contribute to reinforcing intestinal regionalization in vivo. By controlling organoid culture, we demonstrate how these structures can be used to answer questions not readily addressable with the standard, more variable, organoid models.
DOI: aaw9021
Source: https://www.science.org/doi/10.1126/science.aaw9021