This Article Full Text Full Text (PDF) All Versions of this Article: 93/4/372    most recent 01.RES.0000087643.60150.C2v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Voswinckel, R. Articles by Seeger, W. Search for Related Content PubMed PubMed Citation Articles by Voswinckel, R. Articles by Seeger, W. Related Collections Angiogenesis Endothelium/vascular type/nitric oxide Other Vascular biology

(Circulation Research. 2003;93:372.)
© 2003 American Heart Association, Inc.

Integrative Physiology

Circulating Vascular Progenitor Cells Do Not Contribute to Compensatory Lung Growth

Robert Voswinckel, Tibor Ziegelhoeffer, Matthias Heil, Sawa Kostin, Georg Breier, Tanja Mehling, Rainer Haberberger, Matthias Clauss, Andreas Gaumann, Wolfgang Schaper, Werner Seeger

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.

Correspondence to Robert Voswinckel, MD, Medical Clinic 2, University Clinic Giessen, Klinikstrasse 36, 35392 Giessen, Germany. 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

This article has been cited by other articles:

				H. Yoshida, T. Kitaichi, M. Urata, H. Kurobe, T. Kanbara, T. Motoki, and T. Kitagawa Syngeneic bone marrow mononuclear cells improve pulmonary arterial hypertension through vascular endothelial growth factor upregulation. Ann. Thorac. Surg., August 1, 2009; 88(2): 418 - 424. [Abstract] [Full Text] [PDF]

				R. M. Tuder, S. H. Abman, T. Braun, F. Capron, T. Stevens, P. A. Thistlethwaite, and S. G. Haworth Development and pathology of pulmonary hypertension. J. Am. Coll. Cardiol., June 30, 2009; 54(1 Suppl): S3 - S9. [Abstract] [Full Text] [PDF]

				H. Fehrenbach, R. Voswinckel, V. Michl, T. Mehling, A. Fehrenbach, W. Seeger, and J. R. Nyengaard Neoalveolarisation contributes to compensatory lung growth following pneumonectomy in mice Eur. Respir. J., March 1, 2008; 31(3): 515 - 522. [Abstract] [Full Text] [PDF]

				J. Wels, R. N. Kaplan, S. Rafii, and D. Lyden Migratory neighbors and distant invaders: tumor-associated niche cells Genes & Dev., March 1, 2008; 22(5): 559 - 574. [Abstract] [Full Text] [PDF]

				D. J. Nolan, A. Ciarrocchi, A. S. Mellick, J. S. Jaggi, K. Bambino, S. Gupta, E. Heikamp, M. R. McDevitt, D. A. Scheinberg, R. Benezra, et al. Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization Genes & Dev., June 15, 2007; 21(12): 1546 - 1558. [Abstract] [Full Text] [PDF]

				M. H. Hoofnagle, J. A. Thomas, B. R. Wamhoff, and G. K. Owens Origin of Neointimal Smooth Muscle: We've Come Full Circle. Arterioscler Thromb Vasc Biol, December 1, 2006; 26(12): 2579 - 2581. [Full Text] [PDF]

				L. Pardanaud and A. Eichmann Identification, emergence and mobilization of circulating endothelial cells or progenitors in the embryo Development, July 1, 2006; 133(13): 2527 - 2537. [Abstract] [Full Text] [PDF]

				B. Modarai, K.G. Burnand, B. Sawyer, and A. Smith Endothelial Progenitor Cells Are Recruited Into Resolving Venous Thrombi Circulation, May 24, 2005; 111(20): 2645 - 2653. [Abstract] [Full Text] [PDF]

				C. C. W. Hsia Signals and mechanisms of compensatory lung growth J Appl Physiol, November 1, 2004; 97(5): 1992 - 1998. [Abstract] [Full Text] [PDF]

				R. Voswinckel, V. Motejl, A. Fehrenbach, M. Wegmann, T. Mehling, H. Fehrenbach, and W. Seeger Characterisation of post-pneumonectomy lung growth in adult mice Eur. Respir. J., October 1, 2004; 24(4): 524 - 532. [Abstract] [Full Text] [PDF]

				M. Abedin, Y. Tintut, and L. L. Demer Mesenchymal Stem Cells and the Artery Wall Circ. Res., October 1, 2004; 95(7): 671 - 676. [Abstract] [Full Text] [PDF]

				I. Rajantie, M. Ilmonen, A. Alminaite, U. Ozerdem, K. Alitalo, and P. Salven Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells Blood, October 1, 2004; 104(7): 2084 - 2086. [Abstract] [Full Text] [PDF]

				J. R. Gothert, S. E. Gustin, J. A. M. van Eekelen, U. Schmidt, M. A. Hall, S. M. Jane, A. R. Green, B. Gottgens, D. J. Izon, and C. G. Begley Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium Blood, September 15, 2004; 104(6): 1769 - 1777. [Abstract] [Full Text] [PDF]

				T. J. Rabelink, H. C. de Boer, E. J.P. de Koning, and A.-J. van Zonneveld Endothelial Progenitor Cells: More Than an Inflammatory Response? Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 834 - 838. [Abstract] [Full Text]