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Published ahead of print on September 22, 2005, doi:10.1164/rccm.200502-309OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 2, January 2006, 171-179

A more recent version of this article appeared on January 15, 2006
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Submitted on February 25, 2005
Accepted on September 21, 2005

Limited Restoration of Cystic Fibrosis Lung Epithelium in vivo with Adult Marrow Derived Cells

Roberto Loi1, Travis Beckett1, Kaarin K Goncz1, Benjamin T Suratt1, and Daniel J Weiss1*

1 Department of Pulmonary and Critical Care, University of Vermont College of Medicine, Burlington, VT, USA

* To whom correspondence should be addressed. E-mail: dweiss{at}zoo.uvm.edu.

Rationale: Recent literature suggests that adult bone marrow-derived cells can localize to lung and acquire immunophenotypic characteristics of lung epithelial cells. We speculated this might be a potential therapeutic approach for correcting defective lung epithelium in cystic fibrosis. Objective: To determine whether adult marrow-derived cells containing normal cystic fibrosis transmembrane conductance regulator protein (Cftr) could repopulate lung epithelium in transgenic mice deficient in that protein. Methods: Stromal marrow cells or total marrow obtained from adult male wild type mice were transplanted into adult female Cftr knock out mice. To increase marrow cell recruitment naphthalene was used to induce airway epithelial injury in recipient mice. Measurements and Main Results: At one week, one month and three months after transplant, Cftr mRNA was detected in lung homogenates of recipient mice by RT-PCR. Cftr mRNA was not found in either donor marrow cells or in mature circulating leukocytes. In situ examination of recipient mouse lungs demonstrated rare (0.025%) chimeric airway epithelial cells, some of which (0.01%) expressed Cftr protein. Naphthalene-induced airway remodeling nonsignificantly increased the number of chimeric airway epithelial cells expressing Cftr. Conclusions: These results demonstrate that adult marrow cells can be recruited to airway epithelium and induced to express Cftr in mice otherwise lacking this protein. However, the number of observed chimeric epithelial cells is small and new strategies for enhancing airway epithelial remodeling by adult marrow-derived cells will be necessary for correction of defective Cftr-dependent chloride transport.
Key words: stem cell, lung, epithelium, cystic fibrosis, CFTR




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