RT Journal Article
SR Electronic
T1 Late-breaking abstract: Preclinical testing of therapeutic WNT/β-catenin activation in human 3D lung tissue cultures
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P874
VO 44
IS Suppl 58
A1 Franziska Uhl
A1 Sarah Vierkotten
A1 Gerald Burgstaller
A1 Michael Lindner
A1 Oliver Eickelberg
A1 Silke Meiners
A1 Melanie Königshoff
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P874.abstract
AB Inducing repair processes within the adult diseased lung is of major interest. Wnt/β-catenin signal activation has been demonstrated to induce lung repair in emphysemateous mouse lungs in vivo. We aim to determine Wnt/β-catenin driven lung repair processes in the 3D microenvironment, using murine and human diseased lung tissue cultures ex vivo.Vibratome-generated lung slices (300 µm) were viable up to day 7. Lung structure and integrity was determined by 4D confocal live tissue imaging. Lithium chloride (LiCl) stimulation led to active Wnt/β-catenin signaling, as evidenced by increased GFP positive cells in alveolar regions of emphysematous tissue cultures from Wnt TCF-GFP reporter mice. LiCl activated Wnt/β-catenin signaling in tissue cultures of diseased human lungs, as analysed by active β-catenin expression and upregulated target gene expression ex vivo. Wnt/β-catenin signal activation in murine and human tissue cultures was accompanied by altered mRNA and protein expression of alveolar epithelial type I and II cell markers, as analysed by qPCR, Western Blotting, or tissue imaging. We found an increase in T1alpha expression in mouse and human diseased lung tissue cultures. Surfactant protein C expression was significantly upregulated and secreted in human lung tissue cultures from emphysema patients.We demonstrate that human lung tissue cultures are viable, exhibit preserved lung architecture, and express distinct alveolar epithelial marker upon Wnt/β-catenin activation. Human lung tissue cultures represent a valuable tool to analyse potential targets and drugs for lung repair, thereby leading to more translatable and clinically relevant therapeutic options for chronic lung disease.