Circulating vascular progenitor cells do not contribute to compensatory lung growth.
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.
Voswinckel
Robert
R
Department of Internal Medicine, University Clinic Giessen, Giessen, Germany. Robert.Voswinckel@innere.med.uni-giessen.de
Ziegelhoeffer
Tibor
T
Heil
Matthias
M
Kostin
Sawa
S
Breier
Georg
G
Mehling
Tanja
T
Haberberger
Rainer
R
Clauss
Matthias
M
Gaumann
Andreas
A
Schaper
Wolfgang
W
Seeger
Werner
W
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D005838:Genotype; D049452:Green Fluorescent Proteins; D007763:Lac Operon / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D010641:Phenotype; D011650:Pulmonary Alveoli / Q000254:growth & development; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D042787:Receptor, TIE-2; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2