A three-dimensional vessel-on-chip model to study Puumala orthohantavirus pathogenesis,Lab on a Chip

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A three-dimensional vessel-on-chip model to study Puumala orthohantavirus pathogenesis
Lab on a Chip ( IF 6.1 ) Pub Date : 2024-09-18 , DOI: 10.1039/d4lc00543k
Danny Noack ₁ , Anouk van Haperen ₁ , Mirjam C G N van den Hout _{2,

3} , Eleanor M Marshall ₁ , Rosanne W Koutstaal ₁ , Vincent van Duinen ₄ , Lisa Bauer ₁ , Anton Jan van Zonneveld ₄ , Wilfred F J van IJcken _{2,

3} , Marion P G Koopmans ₁ , Barry Rockx ₁

Affiliation

Puumala orthohantavirus (PUUV) infection in humans can result in hemorrhagic fever with renal syndrome. Endothelial cells (ECs) are primarily infected with increased vascular permeability as a central aspect of pathogenesis. Historically, most studies included ECs cultured under static two-dimensional (2D) conditions, thereby not recapitulating the physiological environment due to their lack of flow and inherent pro-inflammatory state. Here, we present a high-throughput model for culturing primary human umbilical vein ECs in 3D vessels-on-chip in which we compared host responses of these ECs to those of static 2D-cultured ECs on a transcriptional level. The phenotype of ECs in vessels-on-chip more closely resembled the in vivo situation due to higher similarity in expression of genes encoding described markers for disease severity and coagulopathy, including IDO1, LGALS3BP, IL6 and PLAT, and more diverse endothelial-leukocyte interactions in the context of PUUV infection. In these vessels-on-chip, PUUV infection did not directly increase vascular permeability, but increased monocyte adhesion. This platform can be used for studying pathogenesis and assessment of possible therapeutics for other endotheliotropic viruses even in high biocontainment facilities.

中文翻译：

用于研究普马拉正汉坦病毒发病机制的三维芯片血管模型

人类感染普马拉正汉坦病毒 (PUUV) 可导致肾综合征出血热。内皮细胞（EC）主要受到血管通透性增加的感染，这是发病机制的一个核心方面。历史上，大多数研究都包括在静态二维 (2D) 条件下培养的 EC，由于缺乏流动和固有的促炎状态，因此无法重现生理环境。在这里，我们提出了一种在 3D 片上血管中培养原代人脐静脉 EC 的高通量模型，其中我们在转录水平上将这些 EC 的宿主反应与静态 2D 培养的 EC 的宿主反应进行了比较。由于编码疾病严重程度和凝血病标记的基因表达具有更高的相似性，包括IDO1 、 LGALS3BP 、 IL6和PLAT ，以及更多样化的内皮细胞-白细胞相互作用，芯片上血管中 EC 的表型更接近体内情况在 PUUV 感染的情况下。在这些芯片上的血管中，PUUV感染并没有直接增加血管通透性，而是增加了单核细胞的粘附。该平台可用于研究其他内皮病毒的发病机制和评估可能的治疗方法，甚至在高度生物防护设施中也是如此。

更新日期：2024-09-19

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