Ferrari Dario, Sengupta Arunima, Heo Lyong, Pethö Laszlo, Michler Johann, Geiser Thomas, de Jesus Perez Vinicio A, Kuebler Wolfgang M, Zeinali Soheila, Guenat Olivier T
Organs-on-chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, Switzerland.
Stanford Center for Genomics and Personalized Medicine, Palo Alto, CA, USA.
iScience. 2023 Feb 13;26(3):106198. doi: 10.1016/j.isci.2023.106198. eCollection 2023 Mar 17.
The endothelium of blood vessels is a vital organ that reacts differently to subtle changes in stiffness and mechanical forces exerted on its environment (extracellular matrix (ECM)). Upon alteration of these biomechanical cues, endothelial cells initiate signaling pathways that govern vascular remodeling. The emerging organs-on-chip technologies allow the mimicking of complex microvasculature networks, identifying the combined or singular effects of these biomechanical or biochemical stimuli. Here, we present a microvasculature-on-chip model to investigate the singular effect of ECM stiffness and mechanical cyclic stretch on vascular development. Following two different approaches for vascular growth, the effect of ECM stiffness on sprouting angiogenesis and the effect of cyclic stretch on endothelial vasculogenesis are studied. Our results indicate that ECM hydrogel stiffness controls the size of the patterned vasculature and the density of sprouting angiogenesis. RNA sequencing shows that the cellular response to stretching is characterized by the upregulation of certain genes such as ANGPTL4+5, PDE1A, and PLEC.
血管内皮是一个重要器官，它对其所处环境（细胞外基质（ECM））的硬度细微变化和施加的机械力会产生不同反应。这些生物力学信号发生改变时，内皮细胞会启动控制血管重塑的信号通路。新兴的芯片器官技术能够模拟复杂的微血管网络，确定这些生物力学或生化刺激的联合或单一作用。在此，我们展示一种芯片微血管模型，以研究ECM硬度和机械循环拉伸对血管发育的单一作用。遵循两种不同的血管生长方法，研究了ECM硬度对发芽血管生成的作用以及循环拉伸对内皮血管生成的作用。我们的结果表明，ECM水凝胶硬度控制着图案化血管的大小和发芽血管生成的密度。RNA测序显示，细胞对拉伸的反应表现为某些基因如ANGPTL4 + 5、PDE1A和PLEC的上调。
