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. 2025 Jul 11;26(14):6665.
doi: 10.3390/ijms26146665.

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

Claudia D'Oria  1   2 , Gilberto Cincinelli  2   3 , Ramona Bason  1   4 , Federica Pisati  5 , Francesca Simoncello  1 , Isabella Scotti  2 , Laura Giudice  2   3 , Ilaria Suardi  2   3 , Paolo Ferrua  6   7 , Chiara Fossati  6   7 , Pietro Simone Randelli  6   7 , Roberto Caporali  2   3 , Massimiliano Pagani  1   4 , Francesca Ingegnoli  2   3
Affiliations

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

Claudia D'Oria et al. Int J Mol Sci. .

Abstract

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.

Keywords: ex vivo model; explants; osteoarthritis; synovium.

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Conflict of interest statement

Author Federica Pisati was employed by the company Cogentech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Osteoarthritis tissue explant cultures maintain both (A) the histologic features as shown by hematoxylin and eosin-stained sections, and (B) the viability as demonstrated by immunohistochemical staining for cleaved caspase 3. Below are two representative patient-derived tissue explants cultured for 10 days (thickness of slices: 4 μm).
Figure 2
Figure 2
Flow cytometry analysis of different cellular components in osteoarthritis tissue explant at different time points: (A) CD8+, CD4+ T cells, and myeloid compartment; (B) sub-lining (CD45-CD90+) and lining (CD45-CD90-CD55+) synoviocytes; and (C) FAP levels in sub-lining and lining synoviocytes expressed as MFI (median fluorescence intensity). Values are expressed as mean with 95% CI (confidence interval).
Figure 3
Figure 3
The gating strategy applied for cell subset identification in flow cytometry analysis.
See this image and copyright information in PMC

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