Advanced pathophysiology mimicking lung models for accelerated drug discovery
2023
The University of Sydney, Sydney, Australia
Respiratory diseases are the 2nd leading cause of death globally, yet current treatments remain insufficient. Due to the lack of reliable lung models that enable rapid, cost-effective, and high-throughput testing, the development of new therapeutics is lengthy and time-consuming. To accelerate this process, the authors established models for both healthy and diseased lungs.
To mimic the lung complexity to different extents, five design components were used: (i) cell type, (ii) membrane structure/constitution, (iii) environmental conditions, (iv) cellular arrangement, (v) substrate, matrix structure and composition. In order to determine whether the lung models are reproducible and reliable, a quality control (QC) strategy was developed, which integrated the real-time and end-point quantitative and qualitative measurements of cellular barrier function, permeability, tight junctions, tissue structure, tissue composition, and cytokine secretion.
The healthy model is characterised by continuous tight junctions, physiological cellular barrier function, a full thickness epithelium composed of multiple cell layers, and the presence of ciliated cells and goblet cells. Meanwhile, the disease model emulates human COPD disease through dysfunctional cellular barrier function, depletion of ciliated cells, and overproduction of goblet cells.
The models developed here have multiple competitive advantages when compared with existing in vitro lung models: (i) the macroscale enables multimodal and correlative characterisation of the same model system, (ii) the use of cells derived from patients that enables the creation of individual models for each patient for personalised medicine, (iii) the use of an extracellular matrix proteins interface, which promotes physiological cell adhesion and differentiation, (iv) media microcirculation that mimics the dynamic conditions in human lungs.
Advanced pathophysiology mimicking lung models for accelerated drug discovery
Wojciech Chrzanowski
Added on: 06-10-2024
[1] https://spj.science.org/doi/10.1186/s40824-023-00366-x
