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Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing.
Lab on a Chip ( IF 6.1 ) Pub Date : 2020-03-23 , DOI: 10.1039/c9lc01097a
Mario Rothbauer 1 , Gregor Höll , Christoph Eilenberger , Sebastian R A Kratz , Bilal Farooq , Patrick Schuller , Isabel Olmos Calvo , Ruth A Byrne , Brigitte Meyer , Birgit Niederreiter , Seta Küpcü , Florian Sevelda , Johannes Holinka , Oliver Hayden , Sandro F Tedde , Hans P Kiener , Peter Ertl
Affiliation  

Rheumatoid arthritis is a chronic, systemic joint disease in which an autoimmune response translates into an inflammatory attack resulting in joint damage, disability and decreased quality of life. Despite recent introduction of therapeutic agents such as anti-TNFα, even the best current therapies fail to achieve disease remission in most arthritis patients. Therefore, research into the mechanisms governing the destructive inflammatory process in rheumatoid arthritis is of great importance and may reveal novel strategies for the therapeutic interventions. To gain deeper insight into its pathogensis, we have developed for the first time a three-dimensional synovium-on-a-chip system in order to monitor the onset and progression of inflammatory synovial tissue responses. In our study, patient-derived primary synovial organoids are cultivated on a single chip platform containing embedded organic-photodetector arrays for over a week in the absence and presence of tumor-necrosis-factor. Using a label-free and non-invasive optical light-scatter biosensing strategy inflammation-induced 3D tissue-level architectural changes were already detected after two days. We demonstrate that the integration of complex human synovial organ cultures in a lab-on-a-chip provides reproducible and reliable information on how systemic stress factors affect synovial tissue architectures.

中文翻译:

使用具有无创性光散射生物传感的三维芯片滑膜监测炎症性关节炎期间的组织水平重塑。

类风湿关节炎是一种慢性全身性关节疾病,其自身免疫反应转化为炎症反应,导致关节损伤,残疾和生活质量下降。尽管最近引入了诸如抗TNFα之类的治疗剂,但即使是目前最好的疗法也无法在大多数关节炎患者中实现疾病缓解。因此,对控制类风湿关节炎破坏性炎症过程的机制的研究具有重要意义,并可能揭示治疗干预的新策略。为了更深入地了解其病因,我们首次开发了一种三维片上滑膜系统,以监测炎症性滑膜组织反应的发生和进展。在我们的研究中 在不存在和存在肿瘤坏死因子的情况下,将患者衍生的初级滑膜类器官在包含嵌入式有机光电探测器阵列的单芯片平台上培养一周以上。使用无标签且非侵入性的光散射生物传感策略,两天后就已经检测到炎症诱导的3D组织级结构变化。我们证明了在芯片实验室中复杂人类滑膜器官文化的整合提供了有关系统性应激因素如何影响滑膜组织结构的可再现和可靠的信息。使用无标签且非侵入性的光散射生物传感策略,两天后就已经检测到炎症诱导的3D组织级结构变化。我们证明了在芯片实验室中复杂人类滑膜器官文化的整合提供了有关系统性应激因素如何影响滑膜组织结构的可再现和可靠的信息。使用无标签且非侵入性的光散射生物传感策略,两天后就已经检测到炎症诱导的3D组织级结构变化。我们证明了在芯片实验室中复杂人类滑膜器官文化的整合提供了有关系统性应激因素如何影响滑膜组织结构的可再现和可靠的信息。
更新日期:2020-04-24
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