Editorial: Exploring Novel In Vitro Models for Cystic Fibrosis Research

Yungcheng Man¹Domenico Mattoscio^2*Roberto Plebani²

• ¹Harvard University Wyss Institute for Biologically Inspired Engineering, Boston, United States
• ²University of Studies G. d'Annunzio Chieti and Pescara, Chieti, Italy

samples derived from individual patients. Their findings demonstrate that, although HNE cells exhibit reduced CFTR functionality compared to bronchial cells, there is a strong correlation in the magnitude of the response to modulators. These critical insights support the use of HNE cells in preclinical drug testing, while also emphasizing the importance of consistency in experiment design, since even small changes in the experimental conditions under which cells are grown or the procedures applied can influence the outcomes. In the context of in vitro CF research models, the establishment of rigorous criteria for experimental design and validation of primary cells assumes particular significance. This is largely due to the necessity of ensuring the reproducibility and clinical significance results, a concern that is further amplified when more complex 3D cultures from patient-derived are employed.Similarly, standardized and validated methods for measuring oxidative stress, a CF hallmark, are needed. In a timely review, Rubin et al. detail a broad range of analytical techniques used to quantify reactive oxygen species, oxidative injury, and antioxidant defenses in CF. The authors reviewed the advantages and limitations of different assays and models and discussed how inconsistencies in experiments may arise. As the field evolves towards the use of multi-parametric readouts in organoid and organ-on-chip platforms, the development of validated, reproducible measures of oxidative stress will be of critical importance to ensure the ability of advanced models to provide clinically relevant information.In summary, the collection of articles in this Research Topic underscores the rapid evolving role of advanced in vitro models in the next era of CF research. The transition from conventional 2D cultures to advanced 3D systems, organoids, and microphysiological systems is a remarkable progress in the development of more predictive and personalized CF models. These advances have the potential to establish a connection between molecular findings and individual therapeutic approaches, thereby accelerating the implementation of personalized CF therapies.