Zarin-Bal Shayan, Passier Margot, Bentley Katie, Ristori Tommaso
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, 5612 AZ, The Netherlands.
Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, 5612 AZ, The Netherlands.
Biochem Soc Trans. 2025 Aug 29;53(4):909-923. doi: 10.1042/BST20253048.
Controlling the formation of new blood vessels, i.e. angiogenesis, is a critical challenge for the success of regenerative medicine. The development of effective strategies is hindered by our incomplete understanding of the dynamic mechanisms involved. During physiological angiogenesis, endothelial cells ensure the formation of a functional vascular network by organizing into phenotypic patterns of tip and stalk cells, as mediated by cell-cell signaling communication. While fundamental research identified the major signaling pathways involved in the tip-stalk selection process, recent studies have highlighted the importance of the temporal dynamics of these signaling pathways in determining the final vascular network topology. In this review, we discuss research studies where synergistic approaches between experimental and computational methods led to a renovated understanding of angiogenesis by revealing new temporal regulators of tip-stalk selection. Next, we present increasing evidence suggesting that mechanical cues, such as extracellular matrix stiffness, cyclic strain, and shear stress, are potential temporal regulators of the dynamics of tip-stalk selection and angiogenesis. Future research focused on this promising direction could enable the development of novel approaches that leverage temporal variations of mechanical cues to steer blood vessel growth.
控制新血管的形成，即血管生成，是再生医学成功的关键挑战。有效策略的开发受到我们对所涉及的动态机制理解不完整的阻碍。在生理性血管生成过程中，内皮细胞通过在细胞间信号通讯介导下组织成尖端细胞和茎细胞的表型模式，确保形成功能性血管网络。虽然基础研究确定了尖端 - 茎细胞选择过程中涉及的主要信号通路，但最近的研究强调了这些信号通路的时间动态在决定最终血管网络拓扑结构方面的重要性。在这篇综述中，我们讨论了实验方法和计算方法之间的协同方法通过揭示尖端 - 茎细胞选择的新时间调节因子，从而对血管生成有了全新理解的研究。接下来，我们提出越来越多的证据表明，机械信号，如细胞外基质硬度、循环应变和剪切应力，是尖端 - 茎细胞选择和血管生成动态的潜在时间调节因子。专注于这个有前景方向的未来研究可能会促成利用机械信号的时间变化来引导血管生长的新方法的开发。
