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Establishment of a human three-dimensional chip-based chondro-synovial coculture joint model for reciprocal cross talk studies in arthritis research
Lab on a Chip ( IF 6.1 ) Pub Date : 2021-09-07 , DOI: 10.1039/d1lc00130b
Mario Rothbauer 1, 2 , Ruth A Byrne 2, 3 , Silvia Schobesberger 2 , Isabel Olmos Calvo 3 , Anita Fischer 1, 3, 4 , Eva I Reihs 1, 2 , Sarah Spitz 2 , Barbara Bachmann 2, 5, 6 , Florian Sevelda 7 , Johannes Holinka 7 , Wolfgang Holnthoner 5, 6 , Heinz Redl 5, 6 , Stefan Toegel 1, 4 , Reinhard Windhager 1, 7 , Hans P Kiener 3 , Peter Ertl 2
Affiliation  

Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane as the joint capsule's inner layer is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, RA's synovial-chondral axis has not yet been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue coculture model that simulates the reciprocal cross talk between individual synovial and chondral organoids. When co-cultivated with synovial organoids, we could demonstrate that chondral organoids induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross talk in the modelling of arthritic diseases.

中文翻译:

基于人体三维芯片的软骨-滑膜共培养联合模型的建立,用于关节炎研究中的相互串扰研究

类风湿性关节炎的特征在于滑膜处进行性的间歇性炎症,最终导致滑膜关节的破坏。作为关节囊内层的滑膜内衬成纤维细胞样滑膜细胞,这些滑膜细胞是支持导致骨侵蚀和软骨破坏的持续性关节炎的关键因素。虽然已经建立了模拟骨源细胞和滑膜细胞之间骨侵蚀分子方面的微流体模型,但尚未使用基于体外人类患者的微流体 3D 模型实现 RA 的滑膜 - 软骨轴文化。因此,我们建立了一个基于芯片的三维组织共培养模型,模拟个体滑膜和软骨类器官之间的相互串扰。当与滑膜类器官共同培养时,我们可以证明软骨类器官诱导更高程度的软骨生理和结构,并与其各自的单一培养物相比显示出不同的细胞因子反应,突出了相互组织水平串扰在关节炎疾病建模中的重要性。
更新日期:2021-09-10
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