Evaluation of the Chemotherapy Drug Response Using Organotypic Cultures of Osteosarcoma Tumours from Mice Models and Canine Patients.

Autor: Brulin B; INSERM, UMR 1238, PHY-OS, Bone Sarcomas and Remodelling of Calcified Tissues, School of Medicine, University of Nantes, 1 rue Gaston Veil, 44035 Nantes, France.; INSERM, UMR 1214, ToNIC, Université Paul Sabatier, CHU Purpan, Pavillon Baudot, Place du Dr Baylac, 31024 Toulouse, France., Nolan JC; Biomedical Engineering, School of Engineering, and the Regenerative Medicine Institute (REMEDI), School of Medicine, National University of Ireland Galway (NUIG), H91 TK33 Galway, Ireland., Marangon T; Biomedical Engineering, School of Engineering, and the Regenerative Medicine Institute (REMEDI), School of Medicine, National University of Ireland Galway (NUIG), H91 TK33 Galway, Ireland., Kovacevic M; Biomedical Engineering, School of Engineering, and the Regenerative Medicine Institute (REMEDI), School of Medicine, National University of Ireland Galway (NUIG), H91 TK33 Galway, Ireland., Chatelais M; INSERM, UMR 1238, PHY-OS, Bone Sarcomas and Remodelling of Calcified Tissues, School of Medicine, University of Nantes, 1 rue Gaston Veil, 44035 Nantes, France., Meheust P; Vetoceane, 9 Allée Alphonse Fillion, 44120 Vertou, France., Abadie J; ONIRIS, Veterinary School of Nantes, 101 Route de Gachet, 44300 Nantes, France., Le Nail LR; INSERM, UMR 1238, PHY-OS, Bone Sarcomas and Remodelling of Calcified Tissues, School of Medicine, University of Nantes, 1 rue Gaston Veil, 44035 Nantes, France.; CHRU Tours, Service de Chirurgie Orthopédique et Traumatologique, Hôpital Trousseau, Université François-Rabelais de Tours, 37044 Tours, France., Rosset P; INSERM, UMR 1238, PHY-OS, Bone Sarcomas and Remodelling of Calcified Tissues, School of Medicine, University of Nantes, 1 rue Gaston Veil, 44035 Nantes, France.; CHRU Tours, Service de Chirurgie Orthopédique et Traumatologique, Hôpital Trousseau, Université François-Rabelais de Tours, 37044 Tours, France., Brennan MÁ; Biomedical Engineering, School of Engineering, and the Regenerative Medicine Institute (REMEDI), School of Medicine, National University of Ireland Galway (NUIG), H91 TK33 Galway, Ireland., Layrolle P; INSERM, UMR 1238, PHY-OS, Bone Sarcomas and Remodelling of Calcified Tissues, School of Medicine, University of Nantes, 1 rue Gaston Veil, 44035 Nantes, France.; INSERM, UMR 1214, ToNIC, Université Paul Sabatier, CHU Purpan, Pavillon Baudot, Place du Dr Baylac, 31024 Toulouse, France.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Sep 29; Vol. 13 (19). Date of Electronic Publication: 2021 Sep 29.
DOI: 10.3390/cancers13194890
Abstrakt: Improvements in the clinical outcome of osteosarcoma have plateaued in recent decades with poor translation between preclinical testing and clinical efficacy. Organotypic cultures retain key features of patient tumours, such as a myriad of cell types organized within an extracellular matrix, thereby presenting a more realistic and personalised screening of chemotherapeutic agents ex vivo. To test this concept for the first time in osteosarcoma, murine and canine osteosarcoma organotypic models were maintained for up to 21 days and in-depth analysis identified proportions of immune and stromal cells present at levels comparable to that reported in vivo in the literature. Cytotoxicity testing of a range of chemotherapeutic drugs (mafosfamide, cisplatin, methotrexate, etoposide, and doxorubicin) on murine organotypic culture ex vivo found limited response to treatment, with immune and stromal cells demonstrating enhanced survival over the global tumour cell population. Furthermore, significantly decreased sensitivity to a range of chemotherapeutics in 3D organotypic culture relative to 2D monolayer was observed, with subsequent investigation confirming reduced sensitivity in 3D than in 2D, even at equivalent levels of drug uptake. Finally, as proof of concept for the application of this model to personalised drug screening, chemotherapy testing with doxorubicin was performed on biopsies obtained from canine osteosarcoma patients. Together, this study highlights the importance of recapitulating the 3D tumour multicellular microenvironment to better predict drug response and provides evidence for the utility and possibilities of organotypic culture for enhanced preclinical selection and evaluation of chemotherapeutics targeting osteosarcoma.
Databáze: MEDLINE
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