Verleden, S. E. | bioRxiv Science

bioRxiv2021

A multiscale X-ray phase-contrast tomography dataset of whole human left lung

Technological advancements in X-ray imaging using bright and coherent synchrotron sources now allows to decouple sample size and resolution, while maintaining high sensitivity to the microstructure of soft, partially dehydrated tissues. The recently developed imaging technique, hierarchical phase-contrast tomography, is a comprehensive approach to address the challenge of organ-scale (up to tens of centimeters) soft tissue imaging with resolution and sensitivity down to the cellular level. Using this technique, we imaged ex vivo an entire human left lung at an isotropic voxel size of 25.08 m along with local zooms down to 6.05 - 6.5 m and 2.45 - 2.5 m in voxel size. The high tissue contrast offered by the fourth-generation synchrotron source at the European Synchrotron Radiation Facility reveals complex multiscale anatomical constitution of the human lung from the macroscopic (centimeter) down to the microscopic (micrometer) scale. The dataset provides complete organ-scale 3D information of the secondary pulmonary lobules and delineates the microstructure of lung nodules with unprecedented detail.

physiology↗

bioRxiv2021

The memory of airway epithelium damage in smokers and COPD patients

RationaleChronic obstructive pulmonary disease (COPD) is a devastating and mostly irreversible lung disease. In COPD, the bronchial epithelium displays several structural and functional abnormalities affecting barrier integrity, cell polarity, and differentiation, as well as epithelial-to-mesenchymal transition and inflammation. Although COPD displays mostly irreversible changes, the (ir)reversible nature of epithelium pathology ex vivo remains poorly known and was the aim of this study. MethodsThe persistence of COPD epithelium abnormalities was addressed in long-term (10 weeks) primary cultures of air/liquid interface-reconstituted airway epithelium from non-smoker controls, smoker controls, and COPD patients. Barrier function, epithelial polarity, cell commitment, epithelial-to-mesenchymal transition and inflammation were assessed in vitro, and certain features were compared in situ to the native epithelium. The role of inflammation was explored by stimulating cultures with a cytokine mix consisting of TNF-, IL-6 and IL-1{beta}. Measurements and main resultsAlmost all epithelial defects (barrier dysfunction, impaired polarity, lineage abnormalities) observed in cells from smokers and COPD patients persisted in vitro up to week 10, except IL-8/CXCL-8 release and epithelial-to-mesenchymal transition which declined over time. Cell lineage and polarity impairments matched abnormalities observed in situ in the surgical samples from which the in vitro epithelium was derived. Cytokine treatment induced COPD-like changes and, in COPD cells, reactivated epithelial-to-mesenchymal transition. ConclusionsThe airway epithelium from smokers and COPD patients displays a memory of its native state and previous injuries by cigarette smoking, which is multidimensional and sustained for extended periods of time.

pathology↗