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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| 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 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850270900033683456 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Monica De Luise |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dcd2efcb9c114a4b9b934ba65ac96d0a |
| institution | OA Journals |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-dcd2efcb9c114a4b9b934ba65ac96d0a2025-08-20T01:52:24ZengNature Portfolionpj Precision Oncology2397-768X2025-05-019111410.1038/s41698-025-00941-6Perfusion-based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironmentMonica De Luise0Ivana Kurelac1Sara Coluccelli2Antonio De Leo3Ewelina M. Bartoszek4Maria Iorio5Marco Grillini6Camelia Alexandra Coadă7Dario de Biase8Lorena Marchio9Mónica Núñez López10Natalie Rimmer11Anna Myriam Perrone12Pierandrea De Iaco13Anna Maria Porcelli14Viola Heinzelmann15Ivan Martin16Francis Jacob17Manuele Giuseppe Muraro18Giuseppe Gasparre19Department of Medical and Surgical Sciences (DIMEC), University of BolognaDepartment of Medical and Surgical Sciences (DIMEC), University of BolognaSolid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di BolognaDepartment of Medical and Surgical Sciences (DIMEC), University of BolognaMicroscopy Core Facility, Department of Biomedicine, University of BaselDepartment of Medical and Surgical Sciences (DIMEC), University of BolognaPathology Unit, IRCCS Azienda Ospedaliero-Universitaria di BolognaDepartment of Medical and Surgical Sciences (DIMEC), University of BolognaSolid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di BolognaDepartment of Medical and Surgical Sciences (DIMEC), University of BolognaOvarian Cancer Research, Department of Biomedicine, University of Basel and University Hospital of BaselOvarian Cancer Research, Department of Biomedicine, University of Basel and University Hospital of BaselDepartment of Medical and Surgical Sciences (DIMEC), University of BolognaDepartment of Medical and Surgical Sciences (DIMEC), University of BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaOvarian Cancer Research, Department of Biomedicine, University of Basel and University Hospital of BaselTissue Engineering, Department of Biomedicine, University of Basel and University Hospital of BaselOvarian Cancer Research, Department of Biomedicine, University of Basel and University Hospital of BaselTissue Engineering, Department of Biomedicine, University of Basel and University Hospital of BaselDepartment of Medical and Surgical Sciences (DIMEC), University of BolognaAbstract 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.https://doi.org/10.1038/s41698-025-00941-6 |
| spellingShingle | 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 Perfusion-based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironment npj Precision Oncology |
| title | Perfusion-based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironment |
| title_full | Perfusion-based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironment |
| title_fullStr | Perfusion-based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironment |
| title_full_unstemmed | Perfusion-based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironment |
| title_short | Perfusion-based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironment |
| title_sort | perfusion based ex vivo culture of frozen ovarian cancer tissues with preserved tumor microenvironment |
| url | https://doi.org/10.1038/s41698-025-00941-6 |
| work_keys_str_mv | AT monicadeluise perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT ivanakurelac perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT saracoluccelli perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT antoniodeleo perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT ewelinambartoszek perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT mariaiorio perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT marcogrillini perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT cameliaalexandracoada perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT dariodebiase perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT lorenamarchio perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT monicanunezlopez perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT natalierimmer perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT annamyriamperrone perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT pierandreadeiaco perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT annamariaporcelli perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT violaheinzelmann perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT ivanmartin perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT francisjacob perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT manuelegiuseppemuraro perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment AT giuseppegasparre perfusionbasedexvivocultureoffrozenovariancancertissueswithpreservedtumormicroenvironment |