Human mature endothelial cells modulate peripheral blood mononuclear cell differentiation toward an endothelial phenotype

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• 作者：Lydia Bellik ; Claudia Musilli ; Maria Cristina Vinci ; Fabrizio Ledda ; Astrid Parenti
• 关键词：Endothelial progenitor cells ; Human coronary endothelium ; Co-culture ; Cell differentiation ; Phenotypical characterization
• 刊名：Experimental Cell Research
• 出版年：2008
• 出版时间：1 October 2008
• 年：2008
• 卷：314
• 期：16
• 页码：2965-2974
• 全文大小：1274 K

文摘

Circulating endothelial progenitor cells (EPCs) can contribute to neovascularization, even if the mechanisms by which they interact with mature endothelial cells remain unclear. The interactions between human coronary artery endothelial cells (HCAECs) and peripheral blood mononuclear cells (PBMCs) during their early differentiation towards an EPC phenotype were investigated. A co-culture model, in which the two cell types share the same culture medium in the absence of any exogenous angiogenic stimulus, was used. The role of hypoxia was assessed by pretreating HCAECs with 3 % O₂ before co-culture setting. Since we have previously shown that both adherent and suspended PBMCs display a significant increase in endothelial marker expression within the 2nd day of culture in an angiogenic environment, the role of HCAECs on early PBMC differentiation was evaluated in both adherent and suspended cell fractions.

A 3-day co-culture period increased the expression of VEGF-R2, VE-cadherin, α_vβ₃- and α₅-integrin in both the adherent and suspended PBMCs, assessed by cytofluorimetric analysis, and up-regulated VEGF-R1 mRNA assessed by real-time RT-PCR. HCAECs influenced PBMC adhesion, transendothelial migration and cell organization on Matrigel. Hypoxia modulated either PBMC differentiation or their functional properties. These data strongly suggest that endothelium may support the differentiation of PBMCs into EPCs.