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

• DOI: 10.1371/journal.pone.0083624
• Publication Date: 2013-12-12T20:16:34Z
• Authors: Xiaopeng Li; Nathan Rossen; Patrick L. Sinn; Andrew L. Hornick; Benjamin R. Steines; Philip H. Karp; Sarah E. Ernst; Ryan J. Adam; Thomas O. Moninger; Dana N. Levasseur; Joseph Zabner
• Keywords: Amniotic epithelial cells; Cell therapy

To develop stem/progenitor cell-based therapy for cystic fibrosis (CF) lung disease, it is first necessary to identify markers of human epithelial progenitor/stem cells and better understand the potential differentiation into distinct lineages. Here we investigated integrin α6β4 as an progenitor cell marker in distal lung. We identified a subpopulation α6β4+ that localized small airways alveolar walls were devoid pro-surfactant protein C expression. The demonstrated key properties stem ex vivo compared α6β4- cells, including higher colony forming efficiency, expression cell-specific transcription factor Nanog, differentiate multiple lineages basal Clara cells. Co-culture with endothelial enhanced proliferation. subset adeno-associated virus (AAVs) serotypes, AAV2 AAV8, capable transducing In addition, reconstitution bronchi from CF patients only 5% normal significantly rescued defects Cl- transport. Therefore, targeting population via either gene delivery or represents new strategy treat disease.