Characterization of porcine circulating progenitor cells: Toward a functional endothelium

Characterization of porcine circulating progenitor cells: Toward a functional endothelium
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DOI:
10.1089/ten.a.2007.0265
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发表时间:
2008-01-01
影响因子:
4.1
通讯作者:
Ameer, Guillermo
Ameer, Guillermo
中科院分区:
医学3区
文献类型:
--
作者:
Allen, Josephine;Khan, Sadiya;Ameer, Guillermo

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缺乏可用的健康血管、显著的患者发病率和高成本阻碍了自体内皮细胞(EC)的成功临床利用。在此,我们评估了使用循环血液中发现的内皮祖细胞(EPC)在聚(1,8-辛二醇-共-柠檬酸盐)(POC)(一种用于血管组织工程的血液相容性和生物可降解弹性体)上构建功能性内皮的可行性。从猪血液中分离出内皮祖细胞,并在体外诱导分化为猪内皮样细胞。一旦分化,EC表型和功能POC进行了评估,根据EC特异性标志物血管性血友病因子,血小板EC粘附分子,血管内皮钙粘蛋白的存在;乙酰化低密度脂蛋白的代谢;抗血栓形成因子一氧化氮和前列环素的分泌;和血小板粘附和凝血过程的抑制在体外。还通过共培养研究了PE样细胞对猪主动脉平滑肌细胞(PASMC)的影响。POC上的PE样细胞的表型、功能和凝血反应与原发性主动脉内皮细胞相似。PE样细胞的存在导致PASMC增殖降低71 +/- 20%;蛋白质:脱氧核糖核酸比率降低52 +/- 2%;以及细长的纺锤形形态,表明从增殖表型转变为收缩表型。这些数据表明,EPCs和POC可以为功能性组织工程化内皮提供基础。
The lack of available healthy vessels, significant patient morbidity, and high costs hinders the successful clinical utilization of autologous endothelial cells (ECs). Herein we assess the feasibility of using endothelial progenitor cells (EPC) found in circulating blood to engineer a functional endothelium on poly(1,8-octanediol-co-citrate) (POC), a hemocompatible and biodegradable elastomer used in vascular tissue engineering. EPCs were isolated from porcine blood and biochemically differentiated into porcine endothelial (PE)-like cells in vitro. Once differentiated, EC phenotype and function on POC were assessed according to the presence of the EC-specific markers von Willebrand factor, platelet EC adhesion molecule, and vascular endothelial cadherin; metabolism of acetylated low-density lipoprotein; secretion of the anti-thrombogenic factors nitric oxide and prostacyclin; and inhibition of platelet adhesion and clotting processes in vitro. The effects of PE-like cells on porcine aortic smooth muscle cells (PASMCs) were also investigated via co-culture. PE-like cells on POC had phenotype, function, and clotting responses similar to those of primary aortic ECs. The presence of PE-like cells resulted in a 71 +/- 20% decrease in PASMC proliferation; a 52 +/- 2% decrease in the protein: deoxyribonucleic acid ratio; and an elongated, spindle-shaped morphology indicative of a shift from the proliferative to the contractile phenotype. These data suggest that EPCs and POC can provide the basis for a functional tissue-engineered endothelium.