A Microfluidic 3D Endothelium-on-a-Chip Model to Study Transendothelial Migration of T Cells in Health and Disease.
A Microfluidic 3D Endothelium-on-a-Chip Model to Study Transendothelial Migration of T Cells in Health and Disease.
复制标题
微流体3D内皮芯片模型研究健康和疾病中T细胞的跨内皮迁移。
DOI：
10.3390/ijms22158234
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发表时间：
2021-07-30
影响因子：
5.6
通讯作者：
van den Broek LJ
中科院分区：
文献类型：
--
作者：
de Haan L;Suijker J;van Roey R;Berges N;Petrova E;Queiroz K;Strijker W;Olivier T;Poeschke O;Garg S;van den Broek LJ
T细胞的募集是机体炎症级联反应的重要组成部分。这个过程涉及T细胞通过血管系统的运输，并稳定地滞留在炎症部位的血管壁，随后是外渗和随后的组织渗透。在这里，我们描述了一种使用高通量、人工无膜微流控平台，允许T细胞畅通无阻地外溢的方法，实时研究流动下的3D T细胞动力学。我们发现，原代人类T细胞在微血管灌流后黏附于内皮血管壁，并可通过肿瘤坏死因子α介导的血管炎症和CXCL12梯度或细胞外基质包埋的黑色素瘤细胞的存在来刺激其进行跨内皮细胞迁移。值得注意的是，迁移行为根据T细胞激活状态的不同而不同。该分析的独特之处在于，它在一个系统中对T细胞贩运、滞留、外渗和迁移进行模拟的全面性，结合其吞吐量、成像质量和易用性。我们设想常规使用这种检测方法来研究免疫学过程，并期望它能促进免疫紊乱、免疫肿瘤学和新型免疫疗法的发展。
The recruitment of T cells is a crucial component in the inflammatory cascade of the body. The process involves the transport of T cells through the vascular system and their stable arrest to vessel walls at the site of inflammation, followed by extravasation and subsequent infiltration into tissue. Here, we describe an assay to study 3D T cell dynamics under flow in real time using a high-throughput, artificial membrane-free microfluidic platform that allows unimpeded extravasation of T cells. We show that primary human T cells adhere to endothelial vessel walls upon perfusion of microvessels and can be stimulated to undergo transendothelial migration (TEM) by TNFα-mediated vascular inflammation and the presence of CXCL12 gradients or ECM-embedded melanoma cells. Notably, migratory behavior was found to differ depending on T cell activation states. The assay is unique in its comprehensiveness for modelling T cell trafficking, arrest, extravasation and migration, all in one system, combined with its throughput, quality of imaging and ease of use. We envision routine use of this assay to study immunological processes and expect it to spur research in the fields of immunological disorders, immuno-oncology and the development of novel immunotherapeutics.
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影响因子：
37.8
作者：
Kircher, Moritz F.;Grimm, Jan;Weissleder, Ralph
通讯作者：
Weissleder, Ralph
影响因子：
7.3
作者：
Benechet AP;Menon M;Khanna KM
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影响因子：
6.5
作者：
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作者：
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Kluger, Martin S.
鞘氨醇 1-磷酸受体 1 通过抑制外周组织 T 淋巴细胞进入传入淋巴管而导致组织滞留
影响因子：
30.5
作者：
Ledgerwood, Levi G.;Lal, Girdhari;Bromberg, Jonathan S.
通讯作者：
Bromberg, Jonathan S.