血管芯片炎症:用于跨内皮电阻和免疫细胞迁移的可扩展平台。
Vascular inflammation on a chip: A scalable platform for trans-endothelial electrical resistance and immune cell migration.
机构信息
Mimetas B.V., Leiden, Netherlands.
Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.
出版信息
Front Immunol. 2023 Jan 24;14:1118624. doi: 10.3389/fimmu.2023.1118624. eCollection 2023.
The vasculature system plays a critical role in inflammation processes in the body. Vascular inflammatory mechanisms are characterized by disruption of blood vessel wall permeability together with increased immune cell recruitment and migration. There is a critical need to develop models that fully recapitulate changes in vascular barrier permeability in response to inflammatory conditions. We developed a scalable platform for parallel measurements of trans epithelial electrical resistance (TEER) in 64 perfused microfluidic HUVEC tubules under inflammatory conditions. Over 250 tubules where exposed to Tumor necrosis factor alpha (TNFα) and interferon gamma (INF-γ) or human peripheral blood mononuclear cells. The inflammatory response was quantified based on changes TEER and expression of ICAM and VE-cadherin. We observed changes in barrier function in the presence of both inflammatory cytokines and human peripheral blood mononuclear cells, characterized by decreased TEER values, increase in ICAM expression as well changes in endothelial morphology. OrganoPlate 3-lane64 based HUVEC tubules provide a valuable tool for inflammatory studies in an automation compatible manner. Continuous TEER measurements enable long term, sensitive assays for barrier studies. We propose the use of our platform as a powerful tool for modelling endothelial inflammation in combination with immune cell interaction that can be used to screen targets and drugs to treat chronic vascular inflammation.
脉管系统在体内炎症过程中起着至关重要的作用。血管炎症机制的特征是破坏血管壁通透性,同时增加免疫细胞募集和迁移。因此,迫切需要开发能够充分模拟血管屏障通透性变化以响应炎症条件的模型。我们开发了一种可扩展的平台,用于在炎症条件下对 64 个灌注微流体 HUVEC 小管中的跨上皮电阻 (TEER) 进行平行测量。超过 250 个小管暴露于肿瘤坏死因子-α (TNFα) 和干扰素-γ (INF-γ) 或人外周血单核细胞。根据 TEER 变化和 ICAM 和 VE-钙黏蛋白的表达来量化炎症反应。我们观察到在存在两种炎症细胞因子和人外周血单核细胞的情况下,屏障功能发生变化,其特征是 TEER 值降低、ICAM 表达增加以及内皮形态变化。OrganoPlate 3-lane64 基于 HUVEC 小管以自动化兼容的方式提供了用于炎症研究的有价值的工具。连续的 TEER 测量能够进行长期、敏感的屏障研究。我们建议将我们的平台用作与免疫细胞相互作用结合的内皮炎症模型的强大工具,可用于筛选治疗慢性血管炎症的靶点和药物。