Laschke Matthias W, Gu Yuan, Menger Michael D
Institute for Clinical and Experimental Surgery, Saarland University, Homburg, Germany.
Front Physiol. 2022 Aug 17;13:981161. doi: 10.3389/fphys.2022.981161. eCollection 2022.
Angiogenesis, the development of new blood vessels from pre-existing ones, is an essential process determining numerous physiological and pathological conditions. Accordingly, there is a high demand for research approaches allowing the investigation of angiogenic mechanisms and the assessment of pro- and anti-angiogenic therapeutics. The present review provides a selective overview and critical discussion of such approaches, which, in line with the 3R principle, all share the common feature that they are not based on animal experiments. They include assays to study the viability, proliferation, migration, tube formation and sprouting activity of endothelial cells in two- and three-dimensional environments, the degradation of extracellular matrix compounds as well as the impact of hemodynamic forces on blood vessel formation. These assays can be complemented by analyses of microvascular network formation in the chorioallantoic membrane assay and early stages of zebrafish larvae. In addition, the combination of experimental data and physical laws enables the mathematical modeling of tissue-specific vascularization, blood flow patterns, interstitial fluid flow as well as oxygen, nutrient and drug distribution. All these animal-free approaches markedly contribute to an improved understanding of fundamental biological mechanisms underlying angiogenesis. Hence, they do not only represent essential tools in basic science but also in early stages of drug development. Moreover, their advancement bears the great potential to analyze angiogenesis in all its complexity and, thus, to make animal experiments superfluous in the future.
血管生成是指从已有的血管发育出新的血管，是决定众多生理和病理状况的一个重要过程。因此，对于能够研究血管生成机制以及评估促血管生成和抗血管生成疗法的研究方法有很高的需求。本综述对这些方法进行了选择性概述和批判性讨论，这些方法符合3R原则，它们的共同特点是不基于动物实验。它们包括在二维和三维环境中研究内皮细胞的活力、增殖、迁移、管形成和芽生活性的试验，细胞外基质化合物的降解以及血流动力学力对血管形成的影响。这些试验可以通过在尿囊膜试验和斑马鱼幼虫早期阶段对微血管网络形成的分析来补充。此外，实验数据和物理定律的结合能够对组织特异性血管化、血流模式、组织液流动以及氧气、营养物质和药物分布进行数学建模。所有这些无动物方法都显著有助于更好地理解血管生成背后的基本生物学机制。因此，它们不仅是基础科学中的重要工具，也是药物开发早期阶段的重要工具。此外，它们的发展具有极大的潜力来全面分析血管生成，从而在未来使动物实验变得多余。
