The incidence of respiratory diseases such as chronic obstructive pulmonary disease and pulmonary cancer is growing significantly around the world, making pulmonary disease one of the leading causes of mortality. However, the development of effective therapeutics for pulmonary diseases has been hindered by the lack of human-mimetic physiological models that reliably emulate patient responses. Recent advances in technology and cell culture have led to the development of organoids and organ-on-a-chip models that allow us to recapitulate the structure, cellular organization, and organ-level responses of the target tissue in vitro. Here, we review the advances and milestones of lung organoid and lung-on-a-chip models in the past decade and highlight their applications in mimicking pulmonary system development, physiology, disease, and regeneration. In addition, we discuss the ongoing challenges and the future prospects of integrating lung organoids and lung-on-a-chip models to overcome current limitations and to enhance their physiological relevance. These human-centric models are likely to provide important insights into pulmonary physiology and pathophysiology for drug discovery that complement and potentially replace traditional animal models.

中文翻译：

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下一代肺部发育、生理学和疾病的临床前模型

慢性阻塞性肺疾病和肺癌等呼吸系统疾病的发病率在世界范围内显着增长，使肺部疾病成为导致死亡的主要原因之一。然而，由于缺乏可靠地模拟患者反应的人体模拟生理模型，肺部疾病有效疗法的发展受到阻碍。技术和细胞培养的最新进展导致类器官和片上器官模型的发展，使我们能够在体外概括目标组织的结构、细胞组织和器官水平反应。在这里，我们回顾了肺类器官和片上肺模型在过去十年中的进展和里程碑，并重点介绍了它们在模拟肺系统发育、生理学、疾病和再生方面的应用。此外，我们讨论了整合肺类器官和片上肺模型以克服当前限制并增强其生理相关性的持续挑战和未来前景。这些以人为中心的模型可能会为药物发现提供肺生理学和病理生理学的重要见解，从而补充并可能取代传统的动物模型。