Wang William Y, Jarman Evan H, Lin Daphne, Baker Brendon M
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States.
Front Bioeng Biotechnol. 2021 Mar 19;9:620128. doi: 10.3389/fbioe.2021.620128. eCollection 2021.
Angiogenesis is a complex, multicellular process that involves bidirectional interactions between extracellular matrix (ECM) and collectively invading endothelial cell (EC) sprouts that extend the microvasculature during development, wound healing, and disease processes. While many aspects of angiogenesis have been well studied, the relationship between endothelial sprout morphology and subsequent neovessel function remains relatively unknown. Here, we investigated how various soluble and physical matrix cues that regulate endothelial sprouting speed and proliferation correspond to changes in sprout morphology, namely, sprout stalk diameter. We found that sprout stalk cells utilize a combination of cytoskeletal forces and proteolysis to physically compact and degrade the surrounding matrix, thus creating sufficient space in three-dimensional (3D) ECM for lateral expansion. As increasing sprout diameter precedes lumenization to generate perfusable neovessels, this work highlights how dynamic endothelial stalk cell-ECM interactions promote the generation of functional neovessels during sprouting angiogenesis to provide insight into the design of vascularized, implantable biomaterials.
血管生成是一个复杂的多细胞过程，涉及细胞外基质（ECM）与集体侵入的内皮细胞（EC）芽之间的双向相互作用，这些芽在发育、伤口愈合和疾病过程中扩展微血管系统。虽然血管生成的许多方面已得到充分研究，但内皮芽形态与随后的新血管功能之间的关系仍然相对未知。在这里，我们研究了调节内皮芽生长速度和增殖的各种可溶性和物理基质线索如何与芽形态的变化相对应，即芽茎直径。我们发现，芽茎细胞利用细胞骨架力和蛋白水解作用来物理压缩和降解周围的基质，从而在三维（3D）ECM中创造足够的空间进行横向扩展。由于芽直径增加先于管腔形成以产生可灌注的新血管，这项工作突出了动态内皮茎细胞与ECM相互作用如何在发芽血管生成过程中促进功能性新血管的生成，从而为血管化、可植入生物材料的设计提供见解。
