Impaired in vivo vasculogenic potential of endothelial progenitor cells in comparison to human umbilical vein endothelial cells in a spheroid-based implantation model
Impaired in vivo vasculogenic potential of endothelial progenitor cells in comparison to human umbilical vein endothelial cells in a spheroid-based implantation model
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DOI：
10.1111/j.1365-2184.2009.00610.x
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发表时间：
2009-08-01
影响因子：
8.5
通讯作者：
Stark, G. B.
中科院分区：
文献类型：
--
作者：
Finkenzeller, G.;Graner, S.;Stark, G. B.
目的：新血管形成是组织工程应用中的一个主要挑战，因为植入大量的移植物而没有足够的血管导致植入细胞的缺氧细胞死亡。克服这一点的有吸引力的治疗方法是基于共植入内皮细胞以产生血管网络。我们已经调查了潜在的人内皮祖细胞（EPC）形成功能性血管在体内直接比较血管衍生的内皮细胞，代表人脐静脉内皮细胞（HUVEC）。材料和方法：内皮祖细胞从人外周血中分离，在体外扩增，并在体外分析的表型和功能参数。内皮祖细胞和人脐静脉内皮细胞在体内血管生成的潜力进行了评估，在异种移植模型中，球状内皮聚集体皮下植入到immunodeficiencemics.Results：内皮祖细胞是无法区分的经典内皮标志物CD 31，血管性血友病因子，VE-钙粘蛋白和血管内皮生长因子-R2的表达方面的人脐静脉内皮细胞，并在他们的能力，内吞乙酰化低密度脂蛋白。此外，内皮祖细胞和HUVEC显示几乎相同的血管生成潜力，在体外基质胶发芽试验评估。然而，在体内，检测到EPCs和HUVECs之间的显著和意想不到的差异。而植入的HUVEC球体引起形成一个稳定的灌注微血管网络，植入EPC球体表现出显着受损的能力，形成血管结构在相同的实验conditions.Conclusion：我们的研究结果表明，血管来源的内皮细胞，如HUVEC是上级的EPC在促进体内血管化的工程组织。
Objectives:Neovascularization represents a major challenge in tissue engineering applications since implantation of voluminous grafts without sufficient vascularity results in hypoxic cell death of implanted cells. An attractive therapeutic approach to overcome this is based on co-implantation of endothelial cells to create vascular networks. We have investigated the potential of human endothelial progenitor cells (EPC) to form functional blood vessels in vivo in direct comparison to vascular-derived endothelial cells, represented by human umbilical vein endothelial cells (HUVEC).Materials and methods:EPCs were isolated from human peripheral blood, expanded in vitro and analysed in vitro for phenotypical and functional parameters. In vivo vasculogenic potential of EPCs and HUVECs was evaluated in a xenograft model where spheroidal endothelial aggregates were implanted subcutaneously into immunodeficient mice.Results:EPCs were indistinguishable from HUVECs in terms of expression of classical endothelial markers CD31, von Willebrand factor, VE-cadherin and vascular endothelial growth factor-R2, and in their ability to endocytose acetylated low-density lipoprotein. Moreover, EPCs and HUVECs displayed almost identical angiogenic potential in vitro, as assessed by in vitro Matrigel sprouting assay. However in vivo, a striking and unexpected difference between EPCs and HUVECs was detected. Whereas implanted HUVEC spheroids gave rise to formation of a stable network of perfused microvessels, implanted EPC spheroids showed significantly impaired ability to form vascular structures under identical experimental conditions.Conclusion:Our results indicate that vascular-derived endothelial cells, such as HUVECs are superior to EPCs in terms of promoting in vivo vascularization of engineered tissues.