在MINERVA 2.0微流控芯片上的器官装置中概括了人类肠道上皮的特征。

IF 6.6 3区 医学 Q1 ENGINEERING, BIOMEDICAL APL Bioengineering Pub Date : 2023-09-19 eCollection Date: 2023-09-01 DOI:10.1063/5.0144862
Francesca Donnaloja, Luca Izzo, Marzia Campanile, Simone Perottoni, Lucia Boeri, Francesca Fanizza, Lorenzo Sardelli, Emanuela Jacchetti, Manuela T Raimondi, Laura Di Rito, Ilaria Craparotta, Marco Bolis, Carmen Giordano, Diego Albani
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引用次数: 0

摘要

我们开发了一种名为MINERVA 2.0的创新型芯片上的微流体组织设备,该设备可通过光学方式访问并适用于串行连接。在本工作中,我们通过计算建模和生物评估,将MINERVA 2.0评估为芯片上的微流体肠道上皮。我们还在串联配置前驱体中测试了MINERVA 2.0,以解决多器官相互作用的复杂性。一旦在我们的设备中进行灌注培养,人类肠道永生Caco-2上皮细胞能够存活至少7 天,并形成具有可检测的紧密连接的三维层(occludin和zonulin-1阳性)。可测量的跨上皮耐药性和FITC-葡聚糖渗透性调节以及粘蛋白-2的表达支持了功能层的发育。通过RNASeq评估,动态培养产生了特定的转录组谱,在静态和动态条件下共有524个转录物失调(191个上调,333个下调)。总的来说,收集到的结果表明,我们的芯片上多器官微流体模型显示了关键的肠道上皮特征,由于其模块化设计,可能是构建可定制的多器官芯片平台的基础。
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Human gut epithelium features recapitulated in MINERVA 2.0 millifluidic organ-on-a-chip device.

We developed an innovative millifluidic organ-on-a-chip device, named MINERVA 2.0, that is optically accessible and suitable to serial connection. In the present work, we evaluated MINERVA 2.0 as millifluidic gut epithelium-on-a-chip by using computational modeling and biological assessment. We also tested MINERVA 2.0 in a serially connected configuration prodromal to address the complexity of multiorgan interaction. Once cultured under perfusion in our device, human gut immortalized Caco-2 epithelial cells were able to survive at least up to 7 days and form a three-dimensional layer with detectable tight junctions (occludin and zonulin-1 positive). Functional layer development was supported by measurable trans-epithelial resistance and FITC-dextran permeability regulation, together with mucin-2 expression. The dynamic culturing led to a specific transcriptomic profile, assessed by RNASeq, with a total of 524 dysregulated transcripts (191 upregulated and 333 downregulated) between static and dynamic condition. Overall, the collected results suggest that our gut-on-a-chip millifluidic model displays key gut epithelium features and, thanks to its modular design, may be the basis to build a customizable multiorgan-on-a-chip platform.

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来源期刊
APL Bioengineering
APL Bioengineering ENGINEERING, BIOMEDICAL-
CiteScore
9.30
自引率
6.70%
发文量
39
审稿时长
19 weeks
期刊介绍: APL Bioengineering is devoted to research at the intersection of biology, physics, and engineering. The journal publishes high-impact manuscripts specific to the understanding and advancement of physics and engineering of biological systems. APL Bioengineering is the new home for the bioengineering and biomedical research communities. APL Bioengineering publishes original research articles, reviews, and perspectives. Topical coverage includes: -Biofabrication and Bioprinting -Biomedical Materials, Sensors, and Imaging -Engineered Living Systems -Cell and Tissue Engineering -Regenerative Medicine -Molecular, Cell, and Tissue Biomechanics -Systems Biology and Computational Biology
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