Cell elongation is key to in silico replication of in vitro vasculogenesis and subsequent remodeling
Cell elongation is key to in silico replication of in vitro vasculogenesis and subsequent remodeling
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DOI：
10.1016/j.ydbio.2005.10.003
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发表时间：
2006-01-01
影响因子：
2.7
通讯作者：
Glazier, JA
中科院分区：
文献类型：
--
作者：
Merks, RMH;Brodsky, SV;Glazier, JA
血管发生是脊椎动物循环系统发育的第一步，是从最初分散的内皮细胞开始的初级血管网络的重新生长。在血管发生的第一阶段，内皮细胞伸长并形成网络状结构，称为初级毛细血管丛，其随后重塑，随着时间的推移，内皮细胞条带之间的空位尺寸变粗。为了将内皮细胞的这种内在形态发生能力与其通过远程指导线索和其他细胞类型的调节分离开来，我们在Matrigel中使用人脐静脉内皮细胞（HUVEC）的体外模型。这种准二维内皮细胞培养模型最接近于胚胎平坦区域（如卵黄囊）的血管发生。一些研究已经使用连续数学模型来探索体外血管发生：这些模型描述了细胞系综，但忽略了内皮细胞的形状和活性表面波动。虽然这些模型最初重现血管样形态，但它们最终稳定为血管“岛”的断开模式。“此外，它们未能再现时间上正确的网络粗化。使用以细胞为中心的计算模型，我们表明，内皮细胞的细长形状是正确的时空模拟稳定的血管网络生长的关键。我们使用时间分辨图像分析对HUVEC培养物验证了我们的模拟结果，并发现我们的模拟定量再现了体外血管生成和随后的体外重塑。(c)2005年爱思唯尔公司All rights reserved.
Vasculogenesis, the de novo growth of the primary vascular network from initially dispersed endothelial cells, is the first step in the development of the circulatory system in vertebrates. In the first stages of vasculogenesis, endothelial cells elongate and form a network-like structure, called the primary capillary plexus, which subsequently remodels, with the size of the vacancies between ribbons of endothelial cells coarsening over time. To isolate such intrinsic morphogenetic ability of endothelial cells from its regulation by long-range guidance cues and additional cell types, we use an in vitro model of human umbilical vein endothelial cells (HUVEC) in Matrigel. This quasi-two-dimensional endothelial cell culture model would most closely correspond to vasculogenesis in flat areas of the embryo like the yolk sac. Several studies have used continuum mathematical models to explore in vitro vasculogenesis: such models describe cell ensembles but ignore the endothelial cells' shapes and active surface fluctuations. While these models initially reproduce vascular-like morphologies, they eventually stabilize into a disconnected pattern of vascular "islands." Also, they fail to reproduce temporally correct network coarsening. Using a cell-centered computational model, we show that the endothelial cells' elongated shape is key to correct spatiotemporal in silico replication of stable vascular network growth. We validate our simulation results against HUVEC cultures using time-resolved image analysis and find that our simulations quantitatively reproduce in vitro vasculogenesis and subsequent in vitro remodeling. (c) 2005 Elsevier Inc. All rights reserved.