Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, M5S 3G8, Canada.
Institute of Biomedical Engineering, University of Toronto, 160 College St., Toronto, M5S 3E1, Canada.
Adv Biol (Weinh). 2021 Nov;5(11):e2101080. doi: 10.1002/adbi.202101080. Epub 2021 Oct 15.
Angiogenesis, the development of new blood vessels from existing vasculature, is a key process in normal development and pathophysiology. In vitro models are necessary for investigating mechanisms of angiogenesis and developing antiangiogenic therapies. Microfluidic cell culture models of angiogenesis are favored for their ability to recapitulate 3D tissue structures and control spatiotemporal aspects of the microenvironments. To capture the angiogenesis process, microfluidic models often include endothelial cells and a fibroblast component. However, the influence of fibroblast organization on resulting angiogenic behavior remains unclear. Here a comparative study of angiogenic sprouting on a microfluidic chip induced by fibroblasts in 2D monolayer, 3D dispersed, and 3D spheroid culture formats, is conducted. Vessel morphology and sprout distribution for each configuration are measured, and these observations are correlated with measurements of secreted factors and numerical simulations of diffusion gradients. The results demonstrate that angiogenic sprouting varies in response to fibroblast organization with correlating variations in secretory profile and secreted factor gradients across the microfluidic device. This study is anticipated to shed light on how sprouting dynamics are mediated by fibroblast configuration such that the microfluidic cell culture design process includes the selection of a fibroblast component where the effects are known and leveraged.
血管生成，即从现有脉管系统中发展出新的血管，是正常发育和病理生理学的关键过程。体外模型对于研究血管生成的机制和开发抗血管生成疗法是必要的。血管生成的微流控细胞培养模型因其能够再现 3D 组织结构和控制微环境的时空方面而受到青睐。为了捕获血管生成过程，微流控模型通常包括内皮细胞和成纤维细胞成分。然而，成纤维细胞组织对最终血管生成行为的影响尚不清楚。在这里，对在 2D 单层、3D 分散和 3D 球体培养形式的成纤维细胞诱导的微流控芯片上的血管生成发芽进行了比较研究。测量了每种构型的血管形态和芽的分布，并将这些观察结果与分泌因子的测量和扩散梯度的数值模拟相关联。结果表明，血管生成发芽会响应成纤维细胞的组织而变化，并且在微流控装置中分泌因子的分泌谱和梯度也会发生相应的变化。这项研究有望阐明发芽动力学是如何被成纤维细胞的构型所介导的，从而使微流控细胞培养设计过程包括选择已知和利用其影响的成纤维细胞成分。
