The main scientific result is the demonstration that iPSC-derived macrophages can be delivered directly into the lung by bronchoscopy without loss of viability or function and can be deployed under clinically relevant conditions in ex-vivo perfused porcine lungs. This establishes, for the first time, a technically feasible and scalable method to locally replace or supplement dysfunctional alveolar macrophages in diseased human lungs (in the future). Combined with the definition of chronic airway infections (in particular non-cystic-fibrosis bronchiectasis) as a suitable first-in-human indication, iMAClung now provides a clear translational pathway for a macrophage-based therapy addressing a major unmet medical need.
The potential impact of these results is substantial. From a medical perspective, iMAClung opens a new class of host-directed therapies for chronic lung infections, which could reduce dependence on antibiotics, counteract antimicrobial resistance and improve long-term lung function and patient quality of life. From a technological perspective, the project establishes a platform for local, tissue-targeted delivery of iPSC-derived immune cells, which can be extended beyond infections to inflammatory, fibrotic and oncological lung diseases. More broadly, the successful integration of iPSC-derived macrophages with existing clinical delivery devices positions this approach as a blueprint for future cell-based therapies in solid organs.
To ensure further uptake and success, several key needs must be addressed. First, additional preclinical research is required to generate comprehensive safety, biodistribution and efficacy data in relevant large-animal and human lung models, in order to support regulatory submissions for first-in-human clinical trials. Second, the cell manufacturing process must be further advanced to GMP-compliant production, including standardisation, batch release criteria and long-term stability testing of the iPSC-derived macrophage product. Third, the bronchoscopy-based delivery procedure should be further optimised and standardised as a medical-device–cell-product combination, including regulatory qualification for its intended therapeutic use.
In parallel, regulatory engagement will remain essential, in particular for defining the requirements for Investigational Medicinal Product Dossiers (IMPDs), clinical trial authorisation and combination-product regulation. Finally, continued protection and expansion of intellectual property, together with access to translational funding and industrial partnerships, will be critical to support clinical development, manufacturing scale-up and eventual market entry.
