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TISSUE-SPECIFIC STEM CELLS |
aJames Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St Paul's Hospital, Vancouver, British Columbia, Canada;
bDepartment of Anesthesiology, Pharmacology and Therapeutics and
cBiomedical Research Centre, University of British Columbia, Vancouver, BC Canada;
dOregon Health and Science University, Portland, Oregon, USA;
eDepartment of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia;
fSchool of Pediatrics and Child Health, University of Western Australia, Nedlands, Western Australia, Australia;
gTelethon Institute for Child Health Research, Subiaco, Western Australia, Australia
Key Words. Epithelium • Tissue-specific stem cell • Human • Asthma
Correspondence: Correspondence: Tillie-Louise Hackett, Ph.D., James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Disease, St Paul's Hospital, 1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada. Telephone: 604-682-2344, ext. 63146; Fax: 604-806-8351; e-mail: thackett{at}mrl.ubc.ca
Received on February 20, 2008;
accepted for publication on July 13, 2008.
First published online in STEM CELLS EXPRESS July 24, 2008.
The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelial cells were obtained from seven nontransplantable healthy lungs and four asthmatic lungs by pronase digestion. SP cells were identified by verapamil-sensitive efflux of the DNA-binding dye Hoechst 33342. Using flow cytometry, CD45– SP, CD45+ SP, and non-SP cells were isolated and sorted. CD45– SP cells made up 0.12% ± 0.01% of the total epithelial cell population in normal airway but 4.1% ± 0.06% of the epithelium in asthmatic airways. All CD45– SP cells showed positive staining for epithelial-specific markers cytokeratin-5, E-cadherin, ZO-1, and p63. CD45– SP cells exhibited stable telomere length and increased colony-forming and proliferative potential, undergoing population expansion for at least 16 consecutive passages. In contrast with non-SP cells, fewer than 100 CD45– SP cells were able to generate a multilayered and differentiated epithelium in air-liquid interface culture. SP cells are present in human tracheobronchial epithelium, exhibit both short- and long-term proliferative potential, and are capable of generation of differentiated epithelium in vitro. The number of SP cells is significantly greater in asthmatic airways, providing evidence of dysregulated resident SP cells in the asthmatic epithelium.
Disclosure of potential conflicts of interest is found at the end of this article.
This article has been cited by other articles:
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  T.-L. Hackett, S. M. Warner, D. Stefanowicz, F. Shaheen, D. V. Pechkovsky, L. A. Murray, R. Argentieri, A. Kicic, S. M. Stick, T. R. Bai, et al. Induction of Epithelial-Mesenchymal Transition in Primary Airway Epithelial Cells from Patients with Asthma by Transforming Growth Factor-{beta}1 Am. J. Respir. Crit. Care Med., July 15, 2009; 180(2): 122 - 133. [Abstract] [Full Text] [PDF]
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