In a short news series, we would like to present the four award-winning projects. The first is the work of Laurien Czichon (Leibniz Research Laboratories for Biotechnology and Artificial Organs, LEBAO), who was honored in the Disease Area Cystic Fibrosis and Bronchiectasis.

Organotypic Lung Model from hiPSC Cells: Focus on Epithelial–Macrophage Interactions

Laurien Czichon and Colleagues Develop a Scalable In Vitro Model to Study Bacterial Infections in CF

The development of physiologically relevant models of the human lung is essential for the precise study of cystic fibrosis (CF). Existing systems – mostly based on animal models or primary cell cultures – have limitations in terms of human relevance, scalability, and the ability to capture complex cellular interactions.

To address this, Laurien Czichon and her team have developed a novel organotypic in vitro lung model called AIRMAC (Autologous Immune Responsive Macrophage Airway Coculture). This system is based on human induced pluripotent stem cells (hiPSCs) and combines CF-relevant respiratory epithelial cells with macrophages derived from the same stem cell source. Both cell types carry either the CFTR mutation background or the isogenic control, allowing disease-specific and cross-cell-type interactions to be investigated in detail for the first time.

The model enables long-term stable co-culture for at least 25 days and demonstrates lateral mobility and clustering behavior of macrophages, similar to that observed in vivo. A particularly noteworthy finding is the interaction between the two cell types: iPSC-derived macrophages exhibit an additional decline in their phagocytic capacity when co-cultured with CFTR-mutant airway epithelial cells – highlighting the high functional relevance of the model.

Current investigations focus on macrophage plasticity and functionality within the AIRMAC system, including transcriptional and secretory analyses, as well as studies on pathogen and mucus uptake depending on time and genotype. This system thus provides a promising platform for studying bacterial infections in the CF context and will in the future also enable therapeutic testing in a humanized and scalable environment.

The remaining award-winning projects from the BREATH network will also be presented in this section over the coming weeks.

Text: BREATH/AB

Foto: privat