Zemani Faouzia, Silvestre Jean-Sébastien, Fauvel-Lafeve Françoise, Bruel Arlette, Vilar José, Bieche Ivan, Laurendeau Ingrid, Galy-Fauroux Isabelle, Fischer Anne Marie, Boisson-Vidal Catherine
INSERM U765, Cardiovascular Research Center, Paris, France.
Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):644-50. doi: 10.1161/ATVBAHA.107.160044. Epub 2008 Jan 31.
As SDF-1 and its cognate receptor CXCR4 play a key role in the survival and mobilization of immature cells, we examined whether preconditioning of endothelial progenitor cells (EPCs) with SDF-1 could further promote their capacity to enhance angiogenesis.
EPC exposure to 100 ng/mL SDF-1 for 30 min induced a proangiogenic phenotype, with cell migration and differentiation into vascular cords in Matrigel and increased their therapeutic potential in a nude mouse model of hindlimb ischemia. This pretreatment enhanced EPC adhesion to activated endothelium in physiological conditions of blood flow by stimulating integrin-mediated EPCs binding to endothelial cells. Pretreated EPCs showed significantly upregulated surface alpha4 and alphaM integrin subunit expression involved in the homing of immature cells to a neovasculature and enhanced FGF-2 and promatrix metalloproteinase (MMP)-2 secretion. All these effects were significantly attenuated by EPC incubation with AMD-3100, a CXCR4 antagonist, by prior HSPGs disruption and by HUVEC incubation with anti-intercellular adhesion molecule1 (ICAM-1) and anti-vascular cell adhesion molecule (VCAM) blocking antibodies. Pretreated EPCs adhered very rapidly (within minutes) and were resistant to shear stresses of up to 2500 s(-1).
SDF-1 pretreatment during EPC expansion stimulates EPC adhesion to endothelial cells and thus augments the efficiency of cell therapy for ischemic vascular diseases.
由于基质细胞衍生因子-1（SDF-1）及其同源受体CXCR4在未成熟细胞的存活和动员中起关键作用，我们研究了用SDF-1预处理内皮祖细胞（EPC）是否能进一步提高其促进血管生成的能力。
EPC暴露于100 ng/mL SDF-1 30分钟可诱导促血管生成表型，使其在基质胶中迁移并分化为血管索，同时增强其在裸鼠后肢缺血模型中的治疗潜力。这种预处理通过刺激整合素介导的EPC与内皮细胞结合，增强了EPC在生理血流条件下对活化内皮的粘附。预处理的EPC显示参与未成熟细胞归巢至新生血管的表面α4和αM整合素亚基表达显著上调，并增强了碱性成纤维细胞生长因子-2（FGF-2）和前基质金属蛋白酶（MMP）-2的分泌。与CXCR4拮抗剂AMD-3100孵育、预先破坏硫酸乙酰肝素蛋白聚糖（HSPGs）以及用抗细胞间粘附分子1（ICAM-1）和抗血管细胞粘附分子（VCAM）阻断抗体孵育人脐静脉内皮细胞（HUVEC）后，所有这些效应均显著减弱。预处理的EPC能非常迅速地（在数分钟内）粘附，并且能抵抗高达2500 s(-1)的剪切应力。
在EPC扩增过程中用SDF-1预处理可刺激EPC与内皮细胞的粘附，从而提高缺血性血管疾病细胞治疗的效率。
