The Vascular Biology Program and Department of Surgery, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Angiogenesis. 2021 Feb;24(1):111-127. doi: 10.1007/s10456-020-09746-6. Epub 2020 Sep 21.
Angiogenesis plays a key role in the pathology of diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. Understanding the driving forces of endothelial cell migration and organization, as well as the time frame of these processes, can elucidate mechanisms of action of important pathological pathways. Herein, we have developed an organ-specific microfluidic platform recapitulating the in vivo angiogenic microenvironment by co-culturing mouse primary brain endothelial cells with brain pericytes in a three-dimensional (3D) collagen scaffold. As a proof of concept, we show that this model can be used for studying the angiogenic process and further comparing the angiogenic properties between two different common inbred mouse strains, C57BL/6J and 129S1/SvlmJ. We further show that the newly discovered angiogenesis-regulating gene Padi2 promotes angiogenesis through Dll4/Notch1 signaling by an on-chip mechanistic study. Analysis of the interplay between primary endothelial cells and pericytes in a 3D microfluidic environment assists in the elucidation of the angiogenic response.
血管生成在癌症、糖尿病性视网膜病变和年龄相关性黄斑变性等疾病的病理中起着关键作用。了解内皮细胞迁移和组织的驱动力，以及这些过程的时间框架，可以阐明重要病理途径的作用机制。在此，我们开发了一种器官特异性微流控平台，通过在三维（3D）胶原支架中共培养小鼠原代脑内皮细胞和脑周细胞，重现体内血管生成微环境。作为概念验证，我们表明该模型可用于研究血管生成过程，并进一步比较两种不同常见近交系小鼠（C57BL/6J 和 129S1/SvlmJ）之间的血管生成特性。我们进一步表明，新发现的血管生成调节基因 Padi2 通过芯片上的机制研究通过 Dll4/Notch1 信号促进血管生成。在 3D 微流控环境中分析原发性内皮细胞和周细胞之间的相互作用有助于阐明血管生成反应。
