Werner Nikos, Junk Stefan, Laufs Ulrich, Link Andreas, Walenta Katrin, Bohm Michael, Nickenig Georg
Klinik und Poliklinik, Innere Medizin III, Universität des Saarlandes, 66421 Homburg/Saar, Germany.
Circ Res. 2003 Jul 25;93(2):e17-24. doi: 10.1161/01.RES.0000083812.30141.74. Epub 2003 Jun 26.
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.
内皮细胞损伤是动脉粥样硬化和血管成形术后再狭窄的一个重要病理生理步骤。加速再内皮化会损害新生内膜形成。我们在动脉损伤小鼠模型中评估了静脉输注内皮祖细胞（EPCs）对再内皮化和新生内膜形成的作用。将源自脾脏的小鼠单核细胞（MNCs）在内皮细胞基础培养基中培养。4天后，共91.8±3.2%的贴壁细胞显示摄取乙酰化低密度脂蛋白（Dil-Ac-LDL）并与凝集素结合。免疫染色和长期培养证实了内皮祖细胞表型。为了确定干细胞输注对再内皮化的影响，在颈动脉内皮损伤后，小鼠静脉内接受荧光标记的源自脾脏的MNCs或体外分化的EPCs。输注的细胞严格局限于损伤部位，凝集素结合证实了内皮细胞表型。仅在脾切除的小鼠中可检测到输注细胞归巢至损伤部位。细胞输注导致再内皮化增强，同时新生内膜形成减少。全身应用源自脾脏的MNCs和EPCs归巢至血管损伤部位，导致再内皮化增强，同时新生内膜形成减少。这些结果为干细胞生物学提供了新的见解，并为血管功能障碍的治疗和血管成形术后再狭窄的预防提供了更多信息。本文全文可在http://www.circresaha.org在线获取。
