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h3DSyn – in vitro modeling of human arthropathies for biomedical research, personalized drug screening and toxicity monitoring (Kyburz Lab)
Figure 1: h3DSyn is a cutting-edge microsynovium which aims to advance the validation process of novel medications for arthropathies by emulating human joint inflammation, thus substantially improving the drug development process in academia or industry and tackling the limited predictive value of existing animal models. This bioprinted synovial organoid originates from primary synovial fibroblasts isolated from an osteoarthritis patient.
Stavros Giaglis, André Tiaden and Simone Häner-Massimi are part of the Kyburz Lab, Experimental Rheumatology, which focusses on the pathogenic mechanisms of inflammatory rheumatic diseases including chronic arthropathies. Due to the limited predictive value of existing animal models in this field, the team recently developed h3DSyn, a cutting-edge microsynovium (see Figure 1), to accurately mimic the physiological and pathological conditions of synovitis.
Creating these organoids from human donor cells or cell type-specific cell lines marks a significant achievement towards the development of a robust synovium-on-chip device, which will more conclusively model the synovial compartment. The ultimate goal is to advance the validation process of novel medications for arthropathies by simulating human joint inflammation. For this achievement, the team has now been awarded an Innosuisse Innovation grant (Innolink: 101.275 IP-LS).
The subsequent phases will entail rigorous testing and analysis of these organoids through stimulation with disease-relevant factors, including proinflammatory cytokines and neutrophil extracellular traps, which have been shown to induce synovitis. Furthermore, stimulation protocols in h3DSyn will be meticulously compared to 2D culture setups and an alternative 3D setup. The ultimate goal is to comprehensively evaluate the synovitis phenotype by thoroughly analyzing the pathohistological characteristics of the stimulated organoids, both with and without anti-rheumatoid arthritis (RA) treatment. This analysis will then be compared to available data on synovial tissue biopsies from active RA patients, ensuring the utmost precision in the results.