Establishment of a human three-dimensional chip-based chondro-synovial co-culture joint model for reciprocal cross-talk studies in arthritis research

Rothbauer, M.; Byrne, R. A.; Schobesberger, S.; Olmos Calvo, I.; Fischer, A.; Reihs, E.; Spitz, S.; Bachmann, B. E. M.; Sevelda, F.; Holinka, J.; Holnthoner, W.; Redl, H.; Toegel, S.; Windhager, R.; Kiener, H. P.; Ertl, P.

doi:10.1101/2021.02.19.431936

bioRxiv · 10.1101/2021.02.19.431936

Establishment of a human three-dimensional chip-based chondro-synovial co-culture joint model for reciprocal cross-talk studies in arthritis research

Rothbauer, M.·Byrne, R. A.·Schobesberger, S.·Olmos Calvo, I.·Fischer, A.·Reihs, E.·Spitz, S.·Bachmann, B. E. M.·Sevelda, F.·Holinka, J.·Holnthoner, W.·Redl, H.·Toegel, S.·Windhager, R.·Kiener, H. P.·Ertl, P.

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Abstract

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, which is the joint capsules 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, RAs synovial-chondral axis has yet not been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue co-culture model that simulates the reciprocal cross-talk between individual synovial and chondral organoids. We now demonstrate that chondral organoids, when co-cultivated with synovial 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.

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Rothbauer, M., Byrne, R. A., Schobesberger, S., Olmos Calvo, I., Fischer, A., Reihs, E., Spitz, S., Bachmann, B. E. M., Sevelda, F., Holinka, J., Holnthoner, W., Redl, H., Toegel, S., Windhager, R., Kiener, H. P., Ertl, P.. 2021-02-19. Establishment of a human three-dimensional chip-based chondro-synovial co-culture joint model for reciprocal cross-talk studies in arthritis research. https://doi.org/10.1101/2021.02.19.431936

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