肺类器官在呼吸系统感染性疾病研究中的应用进展

Research progress of lung organoids in respiratory infectious diseases

类器官是细胞在体外悬浮培养条件下自发形成的具有自我更新能力及相关功能的细胞团,是强大的三维模型,可一定程度再现原始组织的细胞异质性、结构与功能。肺类器官(LOs)由人类多能干细胞或成体干(祖)细胞培养、构建而成,其与免疫细胞共培养可更好地体现肺组织免疫反应及体内感染的全貌。本文对比分析LOs与其他肺部感染性疾病常用研究模型(包括动物模型、二维细胞培养、肺芯片和精确切割肺切片等)的特点,概述LOs的构建方法及其在病毒、细菌、分枝杆菌、隐孢子虫等引起的呼吸系统感染性疾病研究中的应用进展。

Organoids are cell mini-clusters and three-dimensional(3D)micro-organs cultured and spontaneously developed under suspension culture condition in vitro,possessing the abilities of self-organize and differentiate into functional cells.They are powerful,and can partially mimic the cellular heterogeneity,structure and function of the original tissues or organs.Lung organoids(LOs)can be cultured and constructed from human pluripotent stem cells or adult stem/progenitor cells.Co-culture of LOs with immune cells can better reflect the overall picture of the immune response of lung tissue and the full spectrum of infection in vivo.This review compares characteristics of LOs with those common models for respiratory infectious diseases,including animal models,two�dimensional cell culture,lung-on-chip and precision-cut lung slices.We provide an overview of the construction method of LOs and their application progress on respiratory system infectious diseases caused by viruses,bacteria,mycobacteria,cryptosporidium,and other pathogens.