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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月23日

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  • 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

摘要

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.