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血管生成的数学建模。

Mathematical modelling of angiogenesis.

作者信息

Chaplain M A

机构信息

Department of Mathematics, University of Dundee, Scotland, UK.

出版信息

J Neurooncol. 2000 Oct-Nov;50(1-2):37-51. doi: 10.1023/a:1006446020377.

Abstract

Angiogenesis, the formation of blood vessels from a pre-existing vasculature, is a process whereby capillary sprouts are formed in response to externally supplied chemical stimuli. The sprouts then grow and develop, driven initially by endothelial cell migration, and organize themselves into a branched, connected network. Subsequent cell proliferation near the sprout-tips permits further extension of the capillaries and ultimately completes the process. Angiogenesis occurs during embryogenesis, wound healing, arthritis and during the growth of solid tumours. In this article we first of all present a review of a variety of mathematical models which have been used to describe the formation of capillary networks and then focus on a specific recent model which uses novel mathematical modelling techniques to generate both two- and three-dimensional vascular structures. The modelling focusses on key events of angiogenesis such as the migratory response of endothelial cells to exogenous cytokines (tumour angiogenic factors, TAF) secreted by a solid tumour; endothelial cell proliferation; endothelial cell interactions with extracellular matrix macromolecules such as fibronectin; capillary sprout branching and anastomosis. Numerical simulations of the model, using parameter values based on experimental data, are presented and the theoretical structures generated by the model are compared with the morphology of actual capillary networks observed in in vivo experiments. A final conclusions section discusses the use of the mathematical model as a possible angiogenesis assay.

摘要

血管生成,即从预先存在的脉管系统形成血管的过程,是一个毛细血管芽响应外部提供的化学刺激而形成的过程。这些芽随后生长发育,最初由内皮细胞迁移驱动,并自行组织成一个分支相连的网络。随后在芽尖附近的细胞增殖使毛细血管进一步延伸,最终完成这一过程。血管生成发生在胚胎发育、伤口愈合、关节炎以及实体肿瘤生长过程中。在本文中,我们首先对用于描述毛细血管网络形成的各种数学模型进行综述,然后重点关注一个近期的特定模型,该模型使用新颖的数学建模技术生成二维和三维血管结构。该建模聚焦于血管生成的关键事件,如内皮细胞对实体肿瘤分泌的外源性细胞因子(肿瘤血管生成因子,TAF)的迁移反应;内皮细胞增殖;内皮细胞与细胞外基质大分子如纤连蛋白的相互作用;毛细血管芽的分支和吻合。给出了使用基于实验数据的参数值对该模型进行的数值模拟,并将模型生成的理论结构与在体内实验中观察到的实际毛细血管网络形态进行了比较。最后结论部分讨论了将该数学模型用作一种可能的血管生成检测方法的情况。

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