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
IFOM ETS-The AIRC Institute of Molecular Oncology, 20122 Milan, Italy.
Rheumatology Clinic, Department of Rheumatology and Medical Sciences, ASST Gaetano Pini-CTO, 20122 Milan, Italy.
Int J Mol Sci. 2025 Jul 11;26(14):6665. doi: 10.3390/ijms26146665.
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 CD90CD55 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.
骨关节炎(OA)是全球最常见的慢性关节病。OA滑膜炎是一个常见特征,可预测症状的发展和进展以及关节损伤。尽管OA滑膜是新型疗法的靶点,但体外模型的开发仍是一个需要进一步研究的领域。我们旨在建立一种人OA滑膜的三维组织外植体培养模型,该模型能在体外保留原始组织的结构和细胞异质性。我们从7例OA患者中获取组织外植体模型,并将培养时间延长至10天,分别通过免疫组织化学(IHC)和流式细胞术评估其形态和细胞组成。外植体培养物的IHC分析表明,我们的体外系统维持了组织完整性和活力。此外,在我们的模型中,考虑CD4 T细胞、CD8 T细胞和髓样细胞组分时,细胞异质性基本未变。在CD90和CD90CD55组分中未观察到显著变化,这些组分也保持激活状态,FAP表达水平较高即表明了这一点。一种体外OA滑膜组织外植体模型在培养中可维持病理组织完整性10天。这种简单可靠的培养系统可能有助于分析OA疾病的发病机制以及治疗药物的开发和测试。