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Limited Restoration of Cystic Fibrosis Lung Epithelium In Vivo with Adult Bone Marrow–derived Cells

Pulmonary and Critical Care, University of Vermont College of Medicine, Burlington, Vermont

Correspondence and requests for reprints should be addressed to Daniel J. Weiss, M.D., Ph.D., 226 Health Sciences Research Facility, University of Vermont College of Medicine, Burlington, VT 05405. 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 bone 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 knockout mice. To increase marrow cell recruitment naphthalene was used to induce airway epithelial injury in recipient mice.

Measurements and Main Results: At 1 wk, 1 mo, and 3 mo after transplantation, Cftr mRNA was detected in lung homogenates of recipient mice by reverse transcription–polymerase chain reaction. Cftr mRNA was not found in either donor marrow cells or 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 bone marrow–derived cells will be necessary for correction of defective CFTR-dependent chloride transport.

Key Words: cystic fibrosis • cystic fibrosis transmembrane conductance regulator protein • epithelium • lung • stem cell

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