人肺类器官用于肺结核病研究进展及前景

Research progress in and prospects of human lung organoids in pulmonary tuberculosis

结核病是一种由结核分枝杆菌(MTB)引起的传播范围极广的细菌感染性疾病,是主要的致死性传染病之一。传统细胞和动物模型为结核病研究作出了很大贡献,但两者均不能准确模拟人体的生理学过程,在结核病病理研究和药物筛选方面具有许多局限性。类器官作为一种新的研究模型,能够模拟和高度复制源器官的结构和功能,在生物医学领域具有重要的应用前景。人多能干细胞和成体干细胞衍生的人肺类器官已用于多种感染性呼吸系统疾病的研究,特别是在肺结核病研究方面揭开了体外研究的新篇章,在3D水平上揭示了感染早期MTB在宿主体内的适应性、细胞嗜性和宿主反应。人肺类器官模型在构建肉芽肿模型、肺结核病机制研究、共病研究和抗结核药物筛选等方面亦可能具有很好的应用前景,值得进一步探索。

Tuberculosis is a widely spread bacterial infectious disease caused by Mycobacterium tuberculosis(MTB),which is one of the major infectious diseases causing death.Traditionally,animal testing and in vitro cell studies have made great contributions to tuberculosis research.However,studies in both animal models and cell cultures have many limitations in the research of tuberculosis pathology and drug screening,as neither model accurately mimics human physiology.As a new research tool,organoids can mimic and highly reproduce the structure and function of the source organ,which is highly promising in the biomedical field.As a result,human lung organoids generated from human pluripotent stem cells and adult stem cells have been employed to investigate various infec⁃tious respiratory diseases,especially in the research of pulmonary tuberculosis,which has opened a new chapter of in vitro research.Human lung organoids models could recapitulate the interaction between MTB and a variety of epithelial cells,reveal the adaptation and cytotropism of MTB and host response in the early stage of infection.In addition,human lung organoids models may also have a good prospect of application in granuloma model construction,pulmonary tuberculosis mechanism,comorbidity research and anti-tuberculosis drug screening,which is worthy of further exploration.