A Three-Dimensional Human Tissue-Engineered Lung Model to Study Influenza A Infection

Area of Science:

• Biomedical Engineering
• Infectious Disease Research
• 3D Cell Culture Models

Background:

• Influenza A virus (IAV) causes significant global mortality annually.
• Current 2D cell culture models lack the in vivo lung's structural complexity for studying IAV immunopathology.
• A 3D model is needed to recapitulate lung physiology and immune responses.

Purpose of the Study:

• To develop a 3D Human Tissue-Engineered Lung Model (3D-HTLM) for studying IAV.
• To characterize the immunophenotype of 3D-cultured primary human small airway epithelial cells (HSAEpCs) in response to IAV.

Main Methods:

• Constructed a 3D chitosan-collagen scaffold for culturing HSAEpCs at the air-liquid interface (ALI).
• Compared 3D cultures with traditional 2D cultures for viability, morphology, and marker expression.
• Infected 3D cultures with H1N1 and H3N2 influenza A virus strains.

Main Results:

• 3D-cultured HSAEpCs at ALI exhibited enhanced viability and morphology resembling in vivo lower airway epithelium.
• Significant increases in aquaporin-5 and cytokeratin-14 expression were observed in 3D cultures compared to 2D.
• IAV infection in 3D cultures induced distinct changes in marker expression and proinflammatory cytokine release.

Conclusions:

• The 3D-HTLM provides a more physiologically relevant in vitro system for studying IAV.
• This model represents a crucial step towards developing advanced tools for pulmonary research and therapeutics development.