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气道类器官模型作为揭示呼吸系统疾病分子机制和治疗靶点的关键工具:文献综述

Airway Organoid Models as Pivotal Tools for Unraveling Molecular Mechanisms and Therapeutic Targets in Respiratory Diseases: A Literature Review.

作者信息

Jiang Shu-Ping, Lin Bing-Qi, Zhou Xing-Qiang, Li Min-Hua, Feng Zhen-Cheng, Qin Yue-Ying, Lin Shi-Qi, Zhou Zi-Qing, Peng Yang, Li Lian

机构信息

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.

Department of Otorhinolaryngology Head and Neck Surgery, Huizhou Central People's Hospital, Huizhou, People's Republic of China.

出版信息

Ther Clin Risk Manag. 2025 Jun 24;21:975-986. doi: 10.2147/TCRM.S526727. eCollection 2025.

DOI:10.2147/TCRM.S526727
PMID:40584024
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12205757/
Abstract

Respiratory inflammatory and infectious diseases continue to impose a substantial global health burden, compounded by persistent gaps in understanding their pathogenic mechanisms and limited therapeutic advancements. To address these challenges, this review systematically analyzed literature from PubMed, Web of Science, and Scopus databases (2005-2025) to evaluate the evolution and applications of airway organoid models in respiratory disease research. Key findings include: (1) the convergence of traditional culture techniques with advanced methodologies - including 3D matrix embedding, bioprinting and organoids-on-chips technologies - has enabled unprecedented recapitulation of human airway architecture and multicellular interactions; (2) these novel models provide unique insights into disease pathogenesis, host-microbe dynamics, and drug response variability; (3) the inherent capacity to maintain native cellular diversity and disease-associated phenotypes positions airway organoids as crucial platforms for personalized medicine approaches. Collectively, these advances establish airway organoids as transformative tools that bridge conventional in vitro models and clinical reality. Looking ahead, coupling organs-on-chips platforms with microgravity culture and single-cell lineage tracing will catalyze fundamental breakthroughs in respiratory disease research.

摘要

呼吸道炎症性和感染性疾病继续给全球健康带来沉重负担,对其致病机制的理解存在持续差距以及治疗进展有限使这一负担更加复杂。为应对这些挑战,本综述系统分析了来自PubMed、科学网和Scopus数据库(2005 - 2025年)的文献,以评估气道类器官模型在呼吸道疾病研究中的演变和应用。主要发现包括:(1)传统培养技术与先进方法(包括3D基质包埋、生物打印和芯片上类器官技术)的融合,实现了对人类气道结构和多细胞相互作用前所未有的重现;(2)这些新型模型为疾病发病机制、宿主 - 微生物动态以及药物反应变异性提供了独特见解;(3)维持天然细胞多样性和疾病相关表型的内在能力使气道类器官成为个性化医疗方法的关键平台。总体而言,这些进展确立了气道类器官作为连接传统体外模型与临床实际的变革性工具。展望未来,将芯片上器官平台与微重力培养和单细胞谱系追踪相结合,将推动呼吸道疾病研究取得根本性突破。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55be/12205757/9d6fbea1feed/TCRM-21-975-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55be/12205757/f30b26c90f0b/TCRM-21-975-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55be/12205757/9d6fbea1feed/TCRM-21-975-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55be/12205757/f30b26c90f0b/TCRM-21-975-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55be/12205757/9d6fbea1feed/TCRM-21-975-g0002.jpg

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本文引用的文献

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Advances in human organoids-on-chips in biomedical research.生物医学研究中人体芯片类器官的进展。
Life Med. 2023 Feb 21;2(1):lnad007. doi: 10.1093/lifemedi/lnad007. eCollection 2023 Feb.
2
Establishment of nasal and olfactory epithelium organoids for unveiling mechanism of tissue regeneration and pathogenesis of nasal diseases.建立鼻腔和嗅觉上皮类器官以揭示组织再生机制和鼻腔疾病的发病机制。
Cell Mol Life Sci. 2025 Jan 3;82(1):33. doi: 10.1007/s00018-024-05557-w.
3
Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction.
人呼吸道类器官可维持人鼻病毒C的可重复增殖并阐明病毒与宿主的相互作用。
Nat Commun. 2024 Dec 30;15(1):10772. doi: 10.1038/s41467-024-55076-2.
4
Human airway epithelium controls infection via inducible nitric oxide synthase.人类气道上皮通过诱导型一氧化氮合酶控制感染。
Front Immunol. 2024 Dec 3;15:1508727. doi: 10.3389/fimmu.2024.1508727. eCollection 2024.
5
Live imaging of airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread.气道上皮细胞的实时成像显示,黏液纤毛清除功能可调节 SARS-CoV-2 的传播。
Nat Commun. 2024 Nov 2;15(1):9480. doi: 10.1038/s41467-024-53791-4.
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Modeling lung adenocarcinoma metastases using patient-derived organoids.利用患者来源的类器官模型进行肺腺癌转移研究。
Cell Rep Med. 2024 Oct 15;5(10):101777. doi: 10.1016/j.xcrm.2024.101777.
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A novel tubular model to recapitulate features of distal airways: the bronchioid.一种用于概括远端气道特征的新型管状模型:类支气管。
Eur Respir J. 2024 Dec 5;64(6). doi: 10.1183/13993003.00562-2024. Print 2024 Dec.
8
Prime editing functionally corrects cystic fibrosis-causing CFTR mutations in human organoids and airway epithelial cells.碱基编辑技术可在人类类器官和气道上皮细胞中对导致囊性纤维化的 CFTR 突变进行功能校正。
Cell Rep Med. 2024 May 21;5(5):101544. doi: 10.1016/j.xcrm.2024.101544. Epub 2024 May 1.
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