Hinds Monica T, Ma MinHui, Tran Noi, Ensley Ann E, Kladakis Stephanie M, Vartanian Keri B, Markway Brandon D, Nerem Robert M, Hanson Stephen R
Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon 97239, USA.
J Biomed Mater Res A. 2008 Sep;86(3):804-12. doi: 10.1002/jbm.a.31672.
Thrombosis and intimal hyperplasia limit the usefulness of small caliber vascular grafts. While some improvements have been reported for grafts seeded with mature endothelial cells (EC), the harvesting of ECs from autologous sources, for example, veins or adipose tissue, remains problematic. More recently, endothelial progenitor cells (EPCs) have been considered a promising source of ECs because EPCs can be readily isolated from whole blood then rapidly expanded in vitro. Additionally, EPCs are increasingly recognized to play important roles in hemostasis, angiogenesis, and arterial injury repair. However, the characterization of EPCs in relevant animal models remains poorly defined. Accordingly, we have characterized the isolation, growth, and functional characteristics of Baboon EPCs (BaEPCs) to evaluate their potential for an autologous cell source for tissue engineered vascular grafts. BaEPCs were successfully cultured from the peripheral blood with an average population doubling time of 1.17 +/- 0.43 days. While the BaEPCs were positive for typical EC markers of vWF, CD31, VE-cadherin, VEGF-R2, Thrombomodulin, and E-selectin, there was reduced eNOS expression. The BaEPCs cell body and actin filaments align in the direction of flow typical of mature ECs. Thus while the lack of eNOS expression is worthy of investigation, EPCs are an attractive cell source for tissue engineered vascular grafts and the baboon model has great potential for continuing evaluations of these cells.
血栓形成和内膜增生限制了小口径血管移植物的效用。虽然已有报道称接种成熟内皮细胞(EC)的移植物有一些改进,但从自体来源(如静脉或脂肪组织)获取ECs仍然存在问题。最近,内皮祖细胞(EPCs)被认为是一种有前景的ECs来源,因为EPCs可以很容易地从全血中分离出来,然后在体外快速扩增。此外,人们越来越认识到EPCs在止血、血管生成和动脉损伤修复中发挥重要作用。然而,相关动物模型中EPCs的特征仍不清楚。因此,我们对狒狒EPCs(BaEPCs)的分离、生长和功能特性进行了表征,以评估其作为组织工程血管移植物自体细胞来源的潜力。BaEPCs成功地从外周血中培养出来,平均群体倍增时间为1.17±0.43天。虽然BaEPCs对vWF、CD31、VE-钙黏蛋白、VEGF-R2、血栓调节蛋白和E-选择素等典型EC标志物呈阳性,但eNOS表达降低。BaEPCs的细胞体和肌动蛋白丝沿成熟ECs典型的血流方向排列。因此,虽然eNOS表达的缺乏值得研究,但EPCs是组织工程血管移植物有吸引力的细胞来源,狒狒模型在持续评估这些细胞方面具有巨大潜力。