Isolation, Expansion And Characterization Of Lung Epithelial Stem Cells

Principal Investigator(s):

Thaddeus Stappenbeck, M.D., Ph.D. - Pathology and Immunology

Steven L. Brody, M.D. - Medicine

Status: Completed

Center(s): Center for Pediatric Pulmonary Disease

Award Mechanism: Interdisciplinary Research Initiative

Project Period: 2/1/2014 - 1/31/2016

Total Amount: $300,000

Project Summary:

The objective of this proposal is to use new methodologies for the isolation and continuous expansion of lung stem cells to provide patient-specific cells for pathobiology studies and future drug testing. The investigators propose to take advantage of the capacity of the signaling molecule Wnt to activate stem cells that line the air spaces of the lung and are affected by childhood diseases, including asthma, bronchiolitis, cystic fibrosis and surfactant deficiency.

Aims:

•     Whether activating Wnt signaling can expand mouse lung epithelial stem cells from different lung regions will be determined.  Stem cell programs will be characterized as well the capacity of these cells to differentiate into specialized cell types.

•     Whether activating Wnt signaling can expand lung epithelial cells isolated from human donors will be determined. Whether a similar approach can be used to expand and re-differentiate lung cells derived from patients with cystic fibrosis, lung transplantation bronchiolitis obliterans and surfactant deficiency will also be evaluated.

Potential impact:  This research will provide a valuable tool for lung stem cell studies, provide opportunities to investigate the mechanisms of childhood lung diseases, enable future drug testing on cells relevant to these diseases, and ultimately pave the way for personalized therapies.