Journal article
Analysis of Adeno-associated Virus Progenitor Cell Transduction in Mouse Lung
Molecular therapy, Vol.17(2), pp.285-293
02/2009
DOI: 10.1038/mt.2008.248
PMCID: PMC2665184
PMID: 19034263
Abstract
Although recombinant adeno-associated virus (rAAV) has been widely used in lung gene therapy approaches, it remains unclear to what extent commonly used AAV serotypes transduce adult progenitors in the lung. In this study, we evaluated the life span and proliferative capacity of rAAV1-, 2-, and 5-transduced airway cells in mouse lung, using a LacZ-CRE reporter transgenic model and Cre-expressing rAAV. In this model, the expression of CRE recombinase led to permanent genetic marking of transduced cells and their descendants with LacZ. To investigate whether the rAAV-transduced cells included airway progenitors, we injured the airways of rAAV-infected mice with Naphthalene, while simultaneously labeling with 5-bromodeoxyuridine (BrdU) to identify slow-cycling progenitor/stem cells that entered the cell cycle and retained label. Both rAAV5 and rAAV1 vectors were capable of transducing a subset of long-lived Clara cells and alveolar type II (ATII) cells that retained nucleotide label and proliferated following lung injury. Importantly, rAAV1 and 5 appeared to preferentially transduce conducting airway epithelial progenitors that had the capacity to clonally expand, both in culture and
in vivo
following lung injury. These studies suggest that rAAV may be a useful vector for gene targeting of airway stem/progenitor cells.
Details
- Title: Subtitle
- Analysis of Adeno-associated Virus Progenitor Cell Transduction in Mouse Lung
- Creators
- Xiaoming Liu - Department of Anatomy and Cell Biology, College of Medicine, The University of IowaMeihui Luo - Department of Anatomy and Cell Biology, College of Medicine, The University of IowaChenhong Guo - Department of Anatomy and Cell Biology, College of Medicine, The University of IowaZiying Yan - Department of Anatomy and Cell Biology, College of Medicine, The University of IowaYujiong Wang - College of Life Science, Ninxia UniversityDiana CM Lei-Butters - Department of Anatomy and Cell Biology, College of Medicine, The University of IowaJohn F Engelhardt - Department of Anatomy and Cell Biology, College of Medicine, The University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular therapy, Vol.17(2), pp.285-293
- DOI
- 10.1038/mt.2008.248
- PMID
- 19034263
- PMCID
- PMC2665184
- NLM abbreviation
- Mol Ther
- ISSN
- 1525-0016
- eISSN
- 1525-0024
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 02/2009
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025419802771
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