Endothelial differentiation of adipose-derived stem cells from elderly patients with cardiovascular disease.
Endothelial differentiation of adipose-derived stem cells from elderly patients with cardiovascular disease.
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DOI：
10.1089/scd.2010.0152
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发表时间：
2011-06
影响因子：
4
通讯作者：
Ping Zhang;N. Moudgill;E. Hager;N. Tarola;C. Dimatteo;S. McIlhenny;T. Tulenko;P. Dimuzio
中科院分区：
文献类型：
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作者：
Ping Zhang;N. Moudgill;E. Hager;N. Tarola;C. Dimatteo;S. McIlhenny;T. Tulenko;P. Dimuzio
脂肪源性干细胞（ASC）在组织工程和再生方面具有重要的治疗潜力。本研究探讨了从老年患者中分离的ASCs的内皮分化和功能能力。从53名患者（50-89岁）中分离出的ASCs显示，高龄或合并症对干细胞采集没有负面影响;相反，在老年供体（>70岁）中观察到的数量高于年轻供体。在内皮生长培养基-2中培养长达3周的ASCs在基质胶上形成索，并表现出乙酰化低密度脂蛋白和凝集素摄取。进一步刺激血管内皮生长因子和剪切应力上调内皮细胞特异性标志物（CD 31，血管性血友病因子，内皮型一氧化氮合酶，VE-钙粘蛋白）。抑制PI（3）K而不是丝裂原活化蛋白激酶通路阻断了观察到的内皮分化。剪切应力促进了抗血栓形成表型，如组织纤溶酶原激活物和一氧化氮的产生以及纤溶酶原激活物抑制剂-1的抑制所示。剪切应力增加整合素α（5）β（1）的表达，随后增加分化的ASCs与基底膜成分的附着。最后，尽管施加高达9达因的剪切力，但接种在脱细胞静脉移植物上的ASC仍抵抗分离。这些结果表明，（1）高龄和合并症不会对ASC的分离产生负面影响，（2）这些干细胞在整个生命周期中保留了获得关键内皮细胞特征的显著能力。因此，脂肪组织是用于血管组织工程的自体干细胞的实际来源。
Adipose-derived stem cells (ASCs) possess significant therapeutic potential for tissue engineering and regeneration. This study investigates the endothelial differentiation and functional capacity of ASCs isolated from elderly patients. Isolation of ASCs from 53 patients (50-89 years) revealed that advanced age or comorbidity did not negatively impact stem cell harvest; rather, higher numbers were observed in older donors (>70 years) than in younger. ASCs cultured in endothelial growth medium-2 for up to 3 weeks formed cords upon Matrigel and demonstrated acetylated-low-density lipoprotein and lectin uptake. Further stimulation with vascular endothelial growth factor and shear stress upregulated endothelial cell-specific markers (CD31, von Willebrand factor, endothelial nitric oxide synthase, and VE-cadherin). Inhibition of the PI(3)K but not mitogen-activated protein kinase pathway blocked the observed endothelial differentiation. Shear stress promoted an anti-thrombogenic phenotype as demonstrated by production of tissue-plasminogen activator and nitric oxide, and inhibition of plasminogen activator inhibitor-1. Shear stress augmented integrin α(5)β(1) expression and subsequently increased attachment of differentiated ASCs to basement membrane components. Finally, ASCs seeded onto a decellularized vein graft resisted detachment despite application of shear force up to 9 dynes. These results suggest that (1) advanced age and comorbidity do not negatively impact isolation of ASCs, and (2) these stem cells retain significant capacity to acquire key endothelial cell traits throughout life. As such, adipose tissue is a practical source of autologous stem cells for vascular tissue engineering.