Generation of an Induced Pluripotent Stem Cell-Derived Alveolar Type II In Vitro Model to Study Influenza A Virus Infection and Drug Treatments

Lena Gauthier; Hristina Koceva; Yann Bachelot; Rosanne W Koutstaal; Puck B van Kasteren; Marc Thilo Figge; Christian Eggeling; Alexander Sandy Mosig

doi:10.1002/adhm.202405141

Generation of an Induced Pluripotent Stem Cell-Derived Alveolar Type II In Vitro Model to Study Influenza A Virus Infection and Drug Treatments

Adv Healthc Mater. 2025 Dec 30:e05141. doi: 10.1002/adhm.202405141. Online ahead of print.

Authors

Lena Gauthier^{1

2

3}, Hristina Koceva⁴, Yann Bachelot^{5

6}, Rosanne W Koutstaal⁷, Puck B van Kasteren⁷, Marc Thilo Figge^{5

8}, Christian Eggeling^{1

2}, Alexander Sandy Mosig⁴

Affiliations

¹ Institute of Applied Optics and Biophysics, Friedrich Schiller University, Jena, Germany.
² Department Biophysical Imaging, Leibniz Institute of Photonic Technology, Jena, Germany.
³ Section of Experimental Virology, Institute of Medical Microbiology, Jena University Hospital, Jena, Germany.
⁴ Institute Biochemistry II, Research Group Non-Animal Methods in Infection and Inflammation Research, Jena University Hospital, Jena, Germany.
⁵ Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute, Jena, Germany.
⁶ Faculty of Biological Sciences, Friedrich Schiller University, Jena, Germany.
⁷ Center For Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
⁸ Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University, Jena, Germany.

PMID: 41467546
DOI: 10.1002/adhm.202405141

Abstract

Influenza viruses (IVs) represent a significant global health issue, capable of causing seasonal epidemics and occasional pandemics with substantial morbidity and mortality. The emergence of viral resistance further complicates treatment strategies. In this study, induced pluripotent stem cell-derived human alveolar type II (iAT2) cells are used to model influenza A virus (IAV) infection and to assess antiviral responses. Cultured at an air-liquid interface (ALI) in transwell systems, iAT2 cells recapitulate key features of the alveolar epithelium and support productive IAV replication. Upon infection, iAT2 cells mounted an antiviral transcriptional response and exhibited sensitivity to oseltamivir treatment, consistent with its established in vivo efficacy. Together, these findings highlight the utility of iAT2 cells as a scalable, physiologically relevant in vitro model for influenza research and antiviral drug testing. Future applications may include the evaluation of emerging viral strains and the development of personalized antiviral therapies.

Keywords: alveolar type II cells; induced pluripotent stem cells; influenza A viruses; oseltamivir; viral infections.

Abstract

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