Advanced analysis of the cellular bronchial epithelial landscape in end-stage COPD enabled by thoracic surgery translational research

Hintergrund Careful analysis of cellular function and differentiation in the human bronchial epithelium is of crucial importance to understand, treat and prevent disease patterns in chronic lung diseases (CLD, including chronic obstructive lung disease/COPD). To enable the translational research avenues needed to foster this research in thoracic surgery, close collaboration between the surgical departments and the associated laboratories is warranted. By the use of highly standardized cell isolation and long-term culture approaches, primary human bronchial epithelial cells (pHBECs) from non-CLD and end-stage COPD patients can be utilized to mimic clinical conditions, understand disease-relevant pathways and cellular behaviors including underlying basal cell phenotypes.

Material und Methode Over 175 human bronchial tissue samples from end-stage CLD patients undergoing lung transplantation at the Thoracic Surgery Division of the LMU Hospital Munich, Germany between 01.2018-03.2023 were processed at the CPC-M bioArchive, a joint biorepository of the German Center for Lung Research, the LMU Universtiy Hospital, the Asklepios Clinic in Gauting and the Institute for Lung Health and Immunity, Helmholtz Munich. As an example, the present study successfully cultured pHBECs from 4 non-CLD, 3 COPD-II and 4 COPD-IV patients air-liquid-interface and analyzed the epithelial response to relevant environmental nanoparticles (NP) including multiomic analysis (transcriptome, proteome). A time-resolved single cell RNA-seq analysis focused on unique features of basal cell differentiation.

Ergebnis In vitro, the human bronchial neo-epithelium derived from end-stage COPD pHBECs revealed an increased resilience towards NP-induced injury. NP-exposed cultures were characterized by secretory cell proliferation and a reduced amount of multi-ciliated cells. Single cell RNA-seq analysis revealed a novel basal cell population that could drive the hypersecretory phenotype in end-stage COPD derived cultures. The basal cell state was characterized by overrepresentation of canonical airway pathway activation involved in secretory and multi-ciliated cell differentiation.

Schlussfolgerung The thoracic surgery translational research is able to update knowledge about the cellular landscape of the human bronchial epithelium, thus contributing to a better disease understanding in end-stage COPD patients driving therapeutic ideas.

Publication History

Article published online:
21 August 2023