Project Objectives

• Learn the Host Lab’s protocol for generating stable, physiologically relevant iPSC‑derived macrophages (iPSC-Macs).
• Integrate iPSC‑Macs into lung‑on‑chip systems.
• Establish an animal‑free platform for lung colonisation studies.
• Introduce NF‑κB reporters for inflammation tracking.
• Standardise and disseminate the workflow.

3Rs Impact

• Potential to reduce animal experiments of lung bacterial colonization (short-term) and to replace mouse models of lung bacterial colonization (long-term).
• Supports reproducible, human‑relevant experiments, which reduces the need for animal use.

Background

Understanding how resident lung bacteria interact with immune cells is essential for studying respiratory health and disease. At the Home Lab (University Hospital of Bern) extensive effort has been made to characterise the human lung microbiota, as demonstrated with the creation of the LuMiCol culture collection, which has over 300 bacterial isolates, and through the development of a novel macrophage‑based system to screen for inflammation potential. However, the Home Lab now aims to produce an in vitro lung-microbiota on-chip (LMOC) model with resident immune cells, which requires the use of human induced pluripotent stem cell–derived macrophages (iPSC‑Macs).

The Host Lab (Hannover Medical School) are pioneers in the production of standardized iPSC‑Macs, and have transplanted iPSC‑Macs into mouse models. As a result of this knowledge exchange, the Home Lab will learn the method for generating iPSC‑Macs, and then aims to be the first to combine this with an animal-free approach, establishing the LMOC as a model for researching lung bacterial colonisation and inflammation in a controlled, human‑relevant environment, with scalable cellular complexity.