Perfusion-based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironment
Ovarian cancer (OC) poses significant treatment challenges due to late-stage diagnosis and a complex tumor microenvironment contributing to therapy resistance. We optimized a U-CUP perfusion-based bioreactor method to culture patient-derived primary and metastatic OC specimens, demonstrating that perfusion better preserves cancer cell viability and proliferation, both when fresh and slow-frozen tissues were used. Perfused cultures maintained key microenvironment components, including cancer-associated fibroblasts, endothelial and immune cells. Genetic analysis confirmed the retention in culture of tumor-specific driver mutations. We hence challenged ad hoc generated cisplatin-sensitive and resistant OC cells with cisplatin during growth in U-CUP, validating our system for the testing of drug response. Finally, treatment of slow-frozen OC tissues with carboplatin/paclitaxel revealed different degrees of response to treatment, as indicated by variations in tumor necrosis and number of residual PAX8<sup>+</sup> cells, providing the bases for the prompt evaluation of OC standard chemotherapy efficacy in our ex vivo system.
Authors
- Giuseppe Gasparre (ORCID: https://orcid.org/0000-0003-1229-9006)
- Ewelina Magdalena Bartoszek (ORCID: https://orcid.org/0000-0001-5153-9258)
- Antonio De Leo (ORCID: https://orcid.org/0000-0002-3761-5135)
- Anna Myriam Perrone (ORCID: https://orcid.org/0000-0003-3140-4772)
- Manuele Giuseppe Muraro (ORCID: https://orcid.org/0000-0002-4590-1916)
- Anna Maria Porcelli (ORCID: https://orcid.org/0000-0002-6209-0692)
- Francis Jacob (ORCID: https://orcid.org/0000-0002-0446-1942)
- Sara Coluccelli (ORCID: https://orcid.org/0000-0002-1475-4044)
- Maria De Iorio (ORCID: https://orcid.org/0000-0003-3109-0478)
- Monica De Luise (ORCID: https://orcid.org/0000-0002-3486-3985)
- Mónica Núñez López
- Ivana Kurelac (ORCID: https://orcid.org/0000-0002-8364-9985)
- Viola A Heinzelmann-Schwarz (ORCID: https://orcid.org/0000-0002-5613-8629)
- Lorena Marchio
- Marco Grillini (ORCID: https://orcid.org/0000-0003-2506-7239)
- Camelia Alexandra Coadǎ (ORCID: https://orcid.org/0000-0001-8362-6639)
- Iván Martín (ORCID: https://orcid.org/0000-0001-6493-0432)
- Pierandrea De Iaco (ORCID: https://orcid.org/0000-0002-8841-6531)
- Natalie Rimmer
- Dario de Biase
Institutions
- University of Basel (CH)
- University Hospital of Basel (CH)
- Azienda USL di Bologna (IT)
- Department of Biomedicine Basel (CH)
- University of Bologna (IT)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-05-23
- DOI
- https://doi.org/10.1038/s41698-025-00941-6
- Citations
- 4
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 4.18
Funders
- National Science Foundation
- European Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Associazione Italiana per la Ricerca sul Cancro