利用Caco-2球粒芯片微流控平台评估空肠弯曲杆菌胞外囊泡与宿主的相互作用。

IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS
Silvia Tea Calzuola, Jeanne Malet-Villemagne, Debora Pinamonti, Francesco Rizzotto, Céline Henry, Christine Péchaux, Jean Baptiste Blondé, Emmanuel Roy, Marisa Manzano, Goran Lakisic, Sandrine Truchet, Jasmina Vidic
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引用次数: 0

摘要

空肠弯曲杆菌是一种食源性病原体,附着并侵入人肠道上皮细胞。空肠梭菌的细胞外囊泡(EVs)在致病性中起重要作用,但其在侵染宿主肠上皮细胞中的作用尚不清楚。体外模型缺乏组织的复杂性,无法准确复制ev与人肠上皮细胞之间的动态相互作用,而动物感染模型具有物种特异性差异,限制了其翻译相关性,并与伦理问题相关。为了弥补这一空白,我们提出了一个集成了阻抗传感器的微流控平台来监测空肠梭菌EV与人肠上皮Caco-2细胞的相互作用。在该微流控装置中培养Caco-2上皮细胞时,Caco-2上皮细胞自发三维形态发生,形成直径为50 ~ 100 μm的球状结构。MTT实验显示,空肠梭菌分泌组和EVs(感染多重性,MOI 10)在2D平板培养中导致Caco-2细胞活力降低60%。相反,3D Caco-2球体对空肠梭菌分泌毒力因子的细胞毒作用表现出明显增强的抗性。通过阻抗谱和活体显微观察相结合,该平台可以实时监测细胞空间生长,灵敏检测EV与肠上皮细胞的相互作用,突出3D细胞组织的保护作用。该模型的生理学相关性通过TEER测量得到证实,该测量表明弯曲杆菌EVs在细胞旁扩散。所开发的微流控装置是研究宿主-微生物相互作用的一个有前途的平台,可能对胃肠炎的生物医学研究产生广泛的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Assessing Campylobacter jejuni Extracellular Vesicle-Host Interaction Using a Microfluidic Platform with Caco-2 Spheroides-on-Chip.

Campylobacter jejuni is a foodborne pathogen that adheres to and invades the epithelial cells of the human intestinal tract. The extracellular vesicles (EVs) of C. jejuni have an important impact during pathogenicity, but their role in invasion of host intestinal epithelial cells remains largely unknown. In vitro models lack the complexity of tissue and fail to accurately replicate the dynamic interactions between EVs and human intestinal epithelial cells, while animal infection models have species-specific differences that limit their translational relevance and are associated with ethical concerns. To bridge this gap, we propose a microfluidic platform integrated with an impedimetric sensor to monitor C. jejuni EV interactions with human intestinal epithelial Caco-2 cells. When cultured in this microfluidic device, Caco-2 epithelial cells underwent spontaneous 3D morphogenesis into spheroid-like structures with diameters ranging from 50 to 100 μm. Functional assays revealed that the C. jejuni secretome and EVs (multiplicity of infection, MOI 10) caused a 60% reduction in Caco-2 cell viability in 2D plate cultures, as measured by the MTT assay. In contrast, 3D Caco-2 spheroids showed significantly increased resistance to cytotoxic effects of secreted virulence factors of C. jejuni. By combining impedance spectroscopy and live microscopic observation, the platform allowed real-time monitoring of cellular spatial growth and sensitive detection of EV interactions with intestinal epithelial cells, highlighting the protective role of 3D cell organization. The physiological relevance of the model was confirmed by TEER measurements that suggested that Campylobacter EVs diffused paracellularly. The developed microfluidic device is a promising platform for investigating host-microbe interactions and may have a broad impact on biomedical research on gastroenteritis.

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来源期刊
ACS Biomaterials Science & Engineering
ACS Biomaterials Science & Engineering Materials Science-Biomaterials
CiteScore
10.30
自引率
3.40%
发文量
413
期刊介绍: ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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