HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sueblinvong, V. Articles by Weiss, D. J. PubMed Articles by Sueblinvong, V. Articles by Weiss, D. J.

Cord Blood–derived Mesenchymal Stem Cells Can Participate in Lung Epithelial Remodeling In Vivo

¹ Department of Medicine, University of Vermont College of Medicine; and ² Department of Obstetric and Gynecology, Fletcher Allen Heath Care/the University of Vermont College of Medicine, Burlington, Vermont

Correspondence and requests for reprints should be addressed to Daniel J. Weiss, M.D., Ph.D., Department of Medicine, 226 Health Sciences Research Facility, University of Vermont College of Medicine, Burlington, VT 05405. E-mail: dweiss{at}uvm.edu

Recent reports show that adult bone marrow–derived stem cells can localize to and acquire phenotypic and functional markers of lung epithelium. These findings raise the novel possibility of stem cell therapy for chronic lung diseases. However, only small numbers of adult marrow-derived stem cells localize to lung and it is not clear whether these cells will be clinically useful. We have previously shown that mesenchymal stem cells (MSCs) isolated from human cord blood (CB) could be induced to acquire lung epithelial cell phenotype in vitro. We speculated that CB-MSCs could participate in lung regeneration in vivo. CB was obtained from uncomplicated term deliveries at the University of Vermont. Mononuclear cells were isolated by Ficoll gradient. Plastic adherent cells were expanded in culture and characterized as MSCs by flow cytometry. The MSCs were administered by tail vein injection to sublethally irradiated (2 Gy) immunodeficient (NOD/SCID) mice at a dose of 2 x 10⁶ cells/mouse. Control animals received saline. Lungs were harvested at 1 day, 2 weeks, 1 month, and 3 months and were analyzed for human genomic DNA with human Alu (n = 4 for each experimental group). At 1 day, there were increased levels of human Alu sequence in lung tissues compared with control lungs. This level decreased at subsequent time points. Immunofluorescent staining for human b2-microglobulin was performed on lung tissues with human origin cells detected in the airway epithelium at all time points. These data suggest that CB-MSCs might be participating in lung regeneration. We are currently characterizing the phenotype of these cells and exploring other lung injury models to better characterize the participation of CB-MSCs in lung epithelial remodeling. CB may be a potential alternative source of stem cells for use in lung remodeling for chronic lung diseases.

FOOTNOTES

Supported by Postdoctoral Fellowship grant from the Cystic Fibrosis Foundation (V.S.), T32 HL76122 (Vermont Lung Center, Charles Irvin, PI) NIH/NHBLI Multidisciplinary Training in Lung Biology (V.S.), HL081289 from the National Heart Lung and Blood Institute (D.J.W.), Research Grants from the Cystic Fibrosis Foundation (D.J.W.) and the American Lung Association (D.J.W.), and NCRR COBRE P20 RR-155557 (Vermont Lung Center, Charles Irvin, PI).

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form July 19, 2007; accepted in final form October 16, 2007)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sueblinvong, V. Articles by Weiss, D. J. PubMed Articles by Sueblinvong, V. Articles by Weiss, D. J.