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Modelling lung repair in health and disease

Objectif

Acute and chronic lung injury is a major cause of morbidity and mortality worldwide. During physiological repair of the damaged alveolar epithelium transdifferentiation of Alveolar Type II (ATII) cells occurs into Alveolar Type I (ATI) cells. Also, recently identified human multipotent lung stem cells (hLSCs) may participate in repair mechanisms of injured lung tissue by differentiating into multiple cell lineages in the lung. In pathological repair mechanisms, epithelial-mesenchymal transition (EMT) occurs, epithelial cells acquire mesenchymal phenotype, a process that is believed to be associated with aberrant repair and scar formation after epithelial injury. EMT contributes to fibrosis in the lung in both acute and chronic alveolar diseases (e.g. Acute Lung Injury (ALI) and Idiopathic pulmonary fibrosis (IPF). The proposed project aims to investigate the role of Wnt11 in the differentiation of alveolar epithelial cells (AECs) and hLSCs. A tissue engineered 3D lung tissue model has been developed to mimic intercellular interactions in the lung which dramatically alters ligand responses in alveolar epithelium. Preliminary results suggest that in 3D co-culture and in human lung explant cultures Wnt11 promotes Alveolar Type II (ATII) like differentiation and prevents Epithelial-Mesenchymal Transition (EMT) in human small airway epithelium. If our hypothesis is correct we will ascertain whether Wnt11 may have important role in lung tissue regeneration thus marking it as a potential therapeutic target to promote alveolar epithelial repair. The use of hLSC may allow novel 3D tissue engineering solutions to be developed to replace damaged alveolar epithelium.

Appel à propositions

FP7-PEOPLE-2011-IEF
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Coordinateur

THE UNIVERSITY OF BIRMINGHAM
Contribution de l’UE
€ 200 371,80
Adresse
Edgbaston
B15 2TT Birmingham
Royaume-Uni

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Région
West Midlands (England) West Midlands Birmingham
Type d’activité
Higher or Secondary Education Establishments
Contact administratif
May Chung (Ms.)
Liens
Coût total
Aucune donnée