NDLI: Integrin α6β4 Identifies Human Distal Lung Epithelial Progenitor Cells with Potential as a Cell-Based Therapy for Cystic Fibrosis Lung Disease

Content Provider	PubMed Central
Author	Xiaopeng, Li Rossen, Nathan Sinn, Patrick L. Hornick, Andrew L. Steines, Benjamin R. Karp, Philip H. Ernst, Sarah E. Adam, Ryan J. Moninger, Thomas O. Levasseur, Dana N. Joseph, Zabner
Editor	Ahmad, Shama
Copyright Year	2013
Abstract	To develop stem/progenitor cell-based therapy for cystic fibrosis (CF) lung disease, it is first necessary to identify markers of human lung epithelial progenitor/stem cells and to better understand the potential for differentiation into distinct lineages. Here we investigated integrin α6β4 as an epithelial progenitor cell marker in the human distal lung. We identified a subpopulation of α6β4+ cells that localized in distal small airways and alveolar walls and were devoid of pro-surfactant protein C expression. The α6β4+ epithelial cells demonstrated key properties of stem cells ex vivo as compared to α6β4- epithelial cells, including higher colony forming efficiency, expression of stem cell-specific transcription factor Nanog, and the potential to differentiate into multiple distinct lineages including basal and Clara cells. Co-culture of α6β4+ epithelial cells with endothelial cells enhanced proliferation. We identified a subset of adeno-associated virus (AAVs) serotypes, AAV2 and AAV8, capable of transducing α6β4+ cells. In addition, reconstitution of bronchi epithelial cells from CF patients with only 5% normal α6β4+ epithelial cells significantly rescued defects in Cl- transport. Therefore, targeting the α6β4+ epithelial population via either gene delivery or progenitor cell-based reconstitution represents a potential new strategy to treat CF lung disease.
Related Links	http://dx.doi.org/10.1371/journal.pone.0083624
Starting Page	83624
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	12
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-12-12
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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