Chondro-synovial cross-talk in Rheumatoid Arthritis modelling organ on a chip
A beautiful paper from Ertl group at Vienna University of Technology co-culturing synovial and chondral organoids in a joint on a chip to study Rheumatoid Arthritis. They used a compartmentalized chip to establish a cross-talk between Matrigel embedded synovial organoids and chondral organoids embedded in a fibrin gel. It is a comprehensive study trying to optimize the chip that models arthritis.
Results
The authors observed that co-cultivation of chondral and synovial organoids improved the phenotype of chondrocytes within chondral organoids in comparison to chondral monocultures in the absence of synovial fibroblasts. It highlights the importance of tissue-level cross talk in biomedical and biopharmaceutical research.
DigesTable of the paper Rothbauer, M., et al. (2021). “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 21(21): 4128-4143. This paper is reproduced under https://creativecommons.org/licenses/by/4.0/. The image of the chip was edited for better clarity, data in the table and text were compiled and interpreted by AZAR Innovations.
Method
The authors used fibroblast-like synoviocytes and commercial human primary chondrocytes in a PDMS chip with two opposing organoid chambers.
Fabrication: fabrication with PDMS
Sterilization: UV treatment
Cells incorporation: for the generation of organoids, cells in Matrigel and fibrin were injected through the compartments
Perfusion/refreshing
Treatments
On-chip read-outs: end-point microscopy, live-dead staining
Off-chip read-outs: flow cytometry, immuno-histo chemistry, RT-qPCR
Strong points:
+ Long term co-culture
+ Optimization of media and chip for more physiological organoid model
+ The design is simple and has potential for scaling up
Nothing is perfect! The system can also improve:
– The device consists of 5 different layers made of PDMS, very nice material for prototyping but scaling up and suitability in drug research is not preferred
– Only few read outs for the validation
– Manual media refreshment, static culture
Conclusion and outlook
The chondro-synovial model of this study can be developed for investigation of molecular cross talk mechanism between synovial and chondral organoids.
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