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Through co\u2010culture of nsoAlvO and monoAM, we generated organoid\u2010macrophage assembloids, in which both components exhibited enhanced maturation. Comprehensive analyses, including immunostaining, functional assays, and single\u2010cell RNA sequencing, demonstrated that the nsoAlvO and monoAM phenotypically and functionally resemble their native counterparts and engage in dynamic and extensive epithelial\u2010macrophage communications. SSEA\u20101+ club cells were identified as the primary alveolar progenitor cells for nsoAlvO. Influenza virus infection in nsoAlvO revealed differential replicative fitness of H5N1 and H1N1 viruses, which recapitulate their authentic tropism in vivo. Notably, the addition of monoAM reduced H5N1 and H1N1 infection in nsoAlvO, suggesting a protective effect of alveolar macrophages against virus dissemination. These human alveolar organoids and organoid\u2010macrophage assembloids provide universally accessible and physiologically relevant in vitro lung models for biomedical research and translational medicine.<\/jats:p>","DOI":"10.1002\/advs.77093","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:44:50Z","timestamp":1786463090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Generation of Nasal Cell\u2010Derived Human Alveolar Organoids and Organoid\u2010Macrophage Assembloids for in Vitro Lung Modeling"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9503-6396","authenticated-orcid":false,"given":"Man Chun","family":"Chiu","sequence":"first","affiliation":[{"name":"Department of Microbiology School of Clinical Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong China"},{"name":"Centre for Virology Vaccinology 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