用于实时研究活体组织屏障健康状况的微物理系统

Ryan Way, Hayley Templeton, Daniel Ball, Ming-Hao Cheng, Stuart A. Tobet, Thomas Chen
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引用次数: 0

摘要

上皮细胞可形成屏障,保护体内许多不同成分免受外部环境的影响。肠道屏障渗透性增加(肠道渗漏)与多种慢性炎症性疾病有关。由于缺乏既能维持组织的生理环境,又能在各种体外刺激下阐明细胞功能的工具,人们难以理解肠道渗漏的原因,也无法采取有效的干预措施。在这里,我们展示了一种微物理系统,它能在生理环境下长时间实时记录小鼠结肠的屏障通透性。该系统包括一个微流体室;可保存微生物群并在屏障上形成必要氧气梯度的介质成分;以及用于获取经皮层电阻(TEER)的集成传感器电极。我们的研究结果表明,该系统能保持组织活力长达 72 小时。TEER 传感器能区分经胶原酶和低 pH 介质处理后的屏障通透性水平,并能检测组织外植体的不同厚度。Thomas Chen 及其同事设计了一种微物理系统,用于在体外环境的生理条件下研究小鼠肠道上皮组织。利用他们的仪器,他们对经上皮电阻进行了随时间变化的分析,并确定了肠道上皮屏障通透性的变化。
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A microphysiological system for studying barrier health of live tissues in real time
Epithelial cells create barriers that protect many different components in the body from their external environment. Increased gut barrier permeability (leaky gut) has been linked to several chronic inflammatory diseases. Understanding the cause of leaky gut and effective interventions are elusive due to the lack of tools that maintain tissue’s physiological environment while elucidating cellular functions under various stimuli ex vivo. Here we present a microphysiological system that records real-time barrier permeability of mouse colon in a physiological environment over extended durations. The system includes a microfluidic chamber; media composition that preserves microbiome and creates necessary oxygen gradients across the barrier; and integrated sensor electrodes for acquiring transepithelial electrical resistance (TEER). Our results demonstrate that the system can maintain tissue viability for up to 72 h. The TEER sensors can distinguish levels of barrier permeability when treated with collagenase and low pH media and detect different thickness in the tissue explant. Thomas Chen and colleagues design a microphysiological system for the study of intestinal mouse epithelial tissue under physiological conditions in an ex-vivo environment. Using their apparatus they perform a time-dependent analysis of the transepithelial electrical resistance and determine changes in the gut epithelial barrier permeability.
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