Department of Pathology and Laboratory Medicine, University of Vermont Cancer Center, Larner College of Medicine, HSRF Bldg., Rm. 214A, Burlington, VT, 05405, USA.
Histochem Cell Biol. 2021 Feb;155(2):301-308. doi: 10.1007/s00418-020-01955-w. Epub 2021 Jan 18.
The lung is comprised of more than 40 distinct cell types that support a complex 3-dimensional (3D) architecture that is required for efficient lung function. Loss of this proper architecture can accommodate and promote lung disease, highlighting researchers' growing need to analyze lung structures in detail. Additionally, in vivo cellular and molecular response to chemical and physical signals, along with the recapitulation of gene-expression patterns, can be lost during the transition from complex 3D tissues to 2D cell culture systems. Therefore, technologies that allow for the investigation of lung function under normal and disease states utilizing the entirety of the lung architecture are required to generate a complete understanding of these processes. Airway cell-derived organoids that can recapitulate lung structure and function ex vivo while being amenable to experimental manipulation, have provided a new and exciting model system to investigate lung biology. In this perspective, we discuss emerging technologies for culturing lung-derived organoids, techniques to visualize organoids using high-resolution microscopy and the resulting information extracted from organoids supporting research focused on lung function and diseases.
肺由 40 多种不同的细胞类型组成,这些细胞支持着复杂的三维(3D)结构,这是实现高效肺功能所必需的。这种适当的结构的丧失会导致并促进肺部疾病,这突显了研究人员越来越需要详细分析肺部结构。此外,在体内,细胞和分子对化学和物理信号的反应,以及基因表达模式的再现,可能会在从复杂的 3D 组织向 2D 细胞培养系统的转变过程中丢失。因此,需要利用肺结构的全部来研究正常和疾病状态下的肺功能的技术,以生成对这些过程的完整理解。气道细胞衍生的类器官能够在体外再现肺结构和功能,同时易于进行实验操作,为研究肺生物学提供了一个新的令人兴奋的模型系统。在这篇观点文章中,我们讨论了培养肺衍生类器官的新兴技术、使用高分辨率显微镜可视化类器官的技术,以及从支持专注于肺功能和疾病的研究的类器官中提取的信息。