Patient-Derived Explants of Osteoarthritic Synovium as Ex Vivo Model for Preclinical Research.

以骨关节炎滑膜患者来源外植体为体外模型进行临床前研究

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作者:D'Oria Claudia, Cincinelli Gilberto, Bason Ramona, Pisati Federica, Simoncello Francesca, Scotti Isabella, Giudice Laura, Suardi Ilaria, Ferrua Paolo, Fossati Chiara, Randelli Pietro Simone, Caporali Roberto, Pagani Massimiliano, Ingegnoli Francesca
Osteoarthritis (OA) is the most common chronic arthropathy worldwide. OA synovitis is a common feature that predicts the development and progression of symptoms and joint damage. Although the OA synovium is a target for novel therapies, the development of ex vivo models remains an area requiring further research. We aim to develop a 3D tissue explant culture model of human OA synovium that preserves the architecture and cellular heterogeneity of the original tissue in vitro. We derived tissue explant models from seven patients with OA and followed the culture for up to 10 days, assessing their morphology and cellular composition by immunohistochemistry (IHC) and flow cytometry, respectively. IHC analysis of explant cultures showed that tissue integrity and viability were maintained in our in vitro system. Furthermore, cellular heterogeneity was essentially unchanged when considering CD4(+) T cells, CD8(+) T cells, and myeloid fractions in our model. No significant variation was observed in the CD90(+) and CD90(-)CD55(+) fractions, which also maintained an activated state as indicated by high levels of FAP expression. An ex vivo OA synovial tissue explant model can maintain pathological tissue integrity for 10 days in culture. This simple and reliable culture system may be useful for analyzing the pathogenesis of OA disease and for the development and testing of therapeutic drugs.

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