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논문 기본 정보

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학술저널
저자정보
Thanh Huyen Phan (The University of Sydney Sydney Nano Institute Faculty of Medicine and Health Sydney School of Pharmacy) Huaikai Shi (Burns Research and Reconstructive Surgery ANZAC Research Institute Concord Hospital University of Sydney) Christopher E. Denes (The Dr. John and Anne Chong Lab for Functional Genomics Charles Perkins Centre and School of Life & Environmental Sciences The University of Sydney) Alexander J. Cole (Centenary Institute The University of Sydney) Yiwei Wang (Burns Research and Reconstructive Surgery ANZAC Research Institute Concord Hospital University of Sydney) Yuen Yee Cheng (Asbestos Disease Research Institute Concord Hospital) Daniel Hesselson (Centenary Institute The University of Sydney) Susan H. Roelofs (Locsense B.V. Locsense B.V. Enschede) Graham Gregory Neely (The Dr. John and Anne Chong Lab for Functional Genomics Charles Perkins Centre and School of Life & Environmental Sciences The University of Sydney) Jun‑Hyeog Jang (Department of Biochemistry College of Medicine Inha University) Wojciech Chrzanowski (The University of Sydney Sydney Nano Institute Faculty of Medicine and Health Sydney School of Pharmacy)
저널정보
한국생체재료학회 생체재료학회지 생체재료학회지 제27권
발행연도
2023.3
수록면
990 - 1,010 (21page)
DOI
https://doi.org/10.1186/s40824-023-00366-x

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Background Respiratory diseases are the 2nd leading cause of death globally. The current treatments for chronic lung diseases are only supportive. Very few new classes of therapeutics have been introduced for lung diseases in the last 40 years, due to the lack of reliable lung models that enable rapid, cost-effective, and high-throughput testing. To accelerate the development of new therapeutics for lung diseases, we established two classes of lung-mimicking models: (i) healthy, and (ii) diseased lungs – COPD. Methods To establish models that mimic the lung complexity to different extents, we used five design components: (i) cell type, (ii) membrane structure/constitution, (iii) environmental conditions, (iv) cellular arrangement, (v) substrate, matrix structure and composition. To determine whether the lung models are reproducible and reliable, we developed a quality control (QC) strategy, 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. Results The healthy model is characterised by (i) continuous tight junctions, (ii) physiological cellular barrier function, (iii) a full thickness epithelium composed of multiple cell layers, and (iv) the presence of ciliated cells and goblet cells. Meanwhile, the disease model emulates human COPD disease: (i) dysfunctional cellular barrier function, (ii) depletion of ciliated cells, and (ii) 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. Conclusion Our model can be utilised to test safety, efficacy, and superiority of new therapeutics as well as to test toxicity and injury induced by inhaled pollution or pathogens. It is envisaged that these models can also be used to test the protective function of new therapeutics for high-risk patients or workers exposed to occupational hazards.
#Lung-mimicking models #Multimodal characterisation #Physiological relevance #Microcirculation #Extracellular matrix #Patient-derived cell lines #Personalised medicine

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