Journal of Stem Cell Research & Therapy

Integrin α6β4 identifies human distal lung epithelial progenitor cells with potential as a cell-based therapy for cystic fibrosis lung disease

3^rd International Conference and Exhibition on Cell & Gene Therapy

October 27-29, 2014 Embassy Suites Las Vegas, USA

Xiaopeng Li

Accepted Abstracts: J Stem Cell Res Ther

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.

Biography :

Xiaopeng Li is currently a Research Assistant Professor in the Department of Internal Medicine at University of Iowa, USA. He got his medical training in China and obtained his PhD in Physiology at Michigan State University. He was further trained at the University of California, San Francisco where he and his mentor Dr. Hal Chapman identified and isolated distal lung epithelial progenitor cells from murine lungs using integrin α6β4 as a surface maker. After joining the University of Iowa, he expanded these studies to investigate the therapeutic and regenerative potential of distal lung progenitor cells in human lung tissue.