Perfusion-based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironment

Abstract 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, demonstratin...

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Main Authors: Monica De Luise, Ivana Kurelac, Sara Coluccelli, Antonio De Leo, Ewelina M. Bartoszek, Maria Iorio, Marco Grillini, Camelia Alexandra Coadă, Dario de Biase, Lorena Marchio, Mónica Núñez López, Natalie Rimmer, Anna Myriam Perrone, Pierandrea De Iaco, Anna Maria Porcelli, Viola Heinzelmann, Ivan Martin, Francis Jacob, Manuele Giuseppe Muraro, Giuseppe Gasparre
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-00941-6
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Summary:Abstract 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+ cells, providing the bases for the prompt evaluation of OC standard chemotherapy efficacy in our ex vivo system.
ISSN:2397-768X