Angiogenic sprouting and capillary lumen formation modeled by human umbilical vein endothelial cells (HUVEC) in fibrin gels:: the role of fibroblasts and Angiopoietin-1
Angiogenic sprouting and capillary lumen formation modeled by human umbilical vein endothelial cells (HUVEC) in fibrin gels:: the role of fibroblasts and Angiopoietin-1
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DOI：
10.1016/s0026-2862(03)00045-1
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发表时间：
2003-09-01
影响因子：
3.1
通讯作者：
Hughes, CCW
中科院分区：
文献类型：
--
作者：
Nakatsu, MN;Sainson, RCA;Hughes, CCW
血管生成是一个多步骤的过程，在成人的发育和生理和病理生理过程中都至关重要。它涉及内皮细胞（EC）从母体血管萌发，随后迁移、增殖、排列、管形成和吻合到血管。其他船只。几个体外模型试图重现这一复杂的事件序列，并取得了不同程度的成功。我们报告了一种优化的人脐静脉EC方案，其中EC从嵌入纤维蛋白凝胶的珠表面发芽。除血管生成素-1外，成纤维细胞衍生因子促进新生血管的发芽、管腔形成和长期稳定性。通过延时和静止的显微显微镜分析显示，动态血管由“尖端细胞”引导，该细胞将许多过程延伸到凝胶中。在这个细胞后面形成一个管腔，被一层极化EC包围。生长中的芽表达notch 1、notch 4和delta 4，以及下游的notch效应物HESR-1。重要的是，腺病毒可以高效感染细胞而不影响芽的形成，从而允许操纵基因表达。这个改进的模型概括了体内血管生成的所有主要步骤，并为分析这一复杂现象提供了一个强大的模型。(C) 2003 Elsevier Inc.版权所有。
Angiogenesis is a multistep process of critical importance both in development and in physiological and pathophysiological processes in the adult. It involves endothelial cell (EC) sprouting from the parent vessel, followed by migration, proliferation, alignment, tube formation, and anastomosis to. other vessels. Several in vitro models have attempted to recreate this complex sequence of events with varying degrees of success. We report an optimized protocol for human umbilical vein EC in which EC sprout from the surface of beads embedded in fibrin gels. Fibroblast-derived factors, other than Angiopoietin-1, promote sprouting, lumen formation, and long-term stability of neovessels. Analysis by time-lapse and still photomicroscopy demonstrates dynamic vessels guided by a "tip cell" that extends numerous processes into the gel. Behind this cell a lumen forms, surrounded by a single layer of polarized EC. The growing sprouts express notch 1, notch 4, and delta 4, as well as the downstream notch effector HESR-1. Importantly, cells can be infected with adenovirus to high efficiency without compromising sprout formation, thus allowing for manipulation of gene expression. This improved model recapitulates all the major steps of angiogenesis seen in vivo and provides a powerful model for analysis of this complex phenomenon. (C) 2003 Elsevier Inc. All rights reserved.