Published online before print July 24, 2003, doi: 10.1161/01.RES.0000087643.60150.C2
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Submitted on March 17, 2003
Revised on July 10, 2003
Accepted on July 10, 2003
Circulating Vascular Progenitor Cells Do Not Contribute to Compensatory Lung Growth
Robert Voswinckel *;
From the Department of Internal Medicine (R.V., T.M., W.S.), University Clinic Giessen, Giessen, Germany; Departments of Molecular and Cellular Biology & Experimental Cardiology (R.V., T.Z., M.H., S.K., G.B., M.C., A.G., W.S.), Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany; and Department of Anatomy and Cellular Biology (R.H.), University of Giessen, Giessen, Germany.
* To whom correspondence should be addressed. E-mail: Robert.Voswinckel{at}innere.med.uni-giessen.de.
The biological principles that underlie the induction and process of alveolization in the lung as well as the maintenance of the complex lung tissue structure are one of the major obstacles in pulmonary medicine today. Bone marrow-derived cells have been shown to participate in angiogenesis, vascular repair, and remodeling of various organs. We addressed this phenomenon in the lung vasculature of mice in a model of regenerative lung growth. C57BL/6 mice were transplanted with bone marrow from one of three different reporter gene-transgenic strains. flk-1+/lacZ mice, tie-2/lacZ transgenic mice (both exhibiting endothelial cell-specific reporter gene expression), and ubiquitously enhanced green fluorescent protein (eGFP)-expressing mice served as marrow donors. After hematopoietic recovery, compensatory lung growth was induced by unilateral pneumonectomy and led to complete restoration of initial lung volume and surface area. The lungs were consecutively investigated for bone marrow-derived vascular cells by lacZ staining and immunohistochemistry for phenotype identification of vascular cells. lacZ- or eGFP-expressing bone marrow-derived endothelial cells could not be found in microvascular regions of alveolar septa. Single eGFP-positive endothelial cells were detected in pulmonary arteries at very low frequencies, whereas no eGFP-positive vascular smooth muscle cells were observed. In conclusion, we demonstrate in a model of lung growth and alveolization in adult mice the absence of significant bone marrow-derived progenitor cell contribution to the concomitant vascular growth and remodeling processes.
Key words: stem cells • plasticity • vascular endothelium • vascular smooth muscle • alveolization
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