Circulation Research. 2003
Published online before print June 26, 2003, doi: 10.1161/01.RES.0000083812.30141.74
Published online before print June 26, 2003, doi: 10.1161/01.RES.0000083812.30141.74
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Submitted on April 10, 2003
Revised on June 16, 2003
Accepted on June 18, 2003
Intravenous Transfusion of Endothelial Progenitor Cells Reduces Neointima Formation After Vascular Injury
Nikos Werner ;
From the Klinik und Poliklinik, Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.
* To whom correspondence should be addressed. E-mail: nickenig{at}med-in.uni-sb.de.
Endothelial cell damage is one important pathophysiological step of atherosclerosis and restenosis after angioplasty. Accelerated reendothelialization impairs neointima formation. We evaluated the role of intravenously transfused endothelial progenitor cells (EPCs) on reendothelialization and neointima formation in a mouse model of arterial injury. Spleen-derived mouse mononuclear cells (MNCs) were cultured in endothelial basal medium. A total of 91.8±3.2% of adherent cells showed uptake of acetylated low-density lipoprotein (Dil-Ac-LDL) and lectin binding after 4 days. Immunostaining and long-term cultures confirmed the endothelial progenitor phenotype. To determine the effect of stem cell transfusion on reendothelialization, mice received either fluorescent-labeled spleen-derived MNCs or in vitro differentiated EPCs intravenously after endothelial injury of the carotid artery. Transfused cells were strictly restricted to the injury site, and lectin binding confirmed the endothelial phenotype. Homing of transfused cells to the site of injury was only detectable in splenectomized mice. Cell transfusion caused enhanced reendothelialization associated with a reduction of neointima formation. Systemically applied spleen-derived MNCs and EPCs home to the site of vascular injury, resulting in an enhanced reendothelialization associated with decreased neointima formation. These results allow novel insights in stem cell biology and provide additional information for the treatment of vascular dysfunction and prevention of restenosis after angioplasty. The full text of this article is available online at http://www.circresaha.org.
Key words: atherosclerosis • spleen • endothelial progenitor cells • transfusion • neointima
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