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A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment

Elly De Vlieghere (UGent) , Koen Van de Vijver (UGent) , Eva Blondeel (UGent) , Nathan Carpentier, Rouba Ghobeira (UGent) , Jarne Pauwels (UGent) , Sebastian Riemann (UGent) , Manon Minsart (UGent) , Charlotte Fieuws, Johanna Mestach (UGent) , et al.
(2023) BIOMATERIALS RESEARCH. 27(1).
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Abstract
Background Long-term drug evaluation heavily relies upon rodent models. Drug discovery methods to reduce animal models in oncology may include three-dimensional (3D) cellular systems that take into account tumor microenvironment (TME) cell types and biomechanical properties. Methods In this study we reconstructed a 3D tumor using an elastic polymer (acrylate-endcapped urethane-based poly(ethylene glycol) (AUPPEG)) with clinical relevant stiffness. Single cell suspensions from low-grade serous ovarian cancer (LGSOC) patient-derived early passage cultures of cancer cells and cancer-associated fibroblasts (CAF) embedded in a collagen gel were introduced to the AUPPEG scaffold. After self-organization in to a 3D tumor, this model was evaluated by a long-term (> 40 days) exposure to a drug combination of MEK and HSP90 inhibitors. The drug-response results from this long-term in vitro model are compared with drug responses in an orthotopic LGSOC xenograft mouse model. Results The in vitro 3D scaffold LGSOC model mimics the growth ratio and spatial organization of the LGSOC. The AUPPEG scaffold approach allows to test new targeted treatments and monitor long-term drug responses. The results correlate with those of the orthotopic LGSOC xenograft mouse model. Conclusions The mechanically-tunable scaffolds colonized by a three-dimensional LGSOC allow long-term drug evaluation and can be considered as a valid alternative to reduce, replace and refine animal models in drug discovery.
Keywords
Biomedical Engineering, Biomaterials, Medicine (miscellaneous), Ceramics and Composites, Stiffness, Micro-environment, Pre-clinical, Drug evaluation, Long-term, 3D cancer model

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Citation

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MLA
De Vlieghere, Elly, et al. “A Preclinical Platform for Assessing Long-Term Drug Efficacy Exploiting Mechanically Tunable Scaffolds Colonized by a Three-Dimensional Tumor Microenvironment.” BIOMATERIALS RESEARCH, vol. 27, no. 1, 2023, doi:10.1186/s40824-023-00441-3.
APA
De Vlieghere, E., Van de Vijver, K., Blondeel, E., Carpentier, N., Ghobeira, R., Pauwels, J., … De Wever, O. (2023). A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment. BIOMATERIALS RESEARCH, 27(1). https://doi.org/10.1186/s40824-023-00441-3
Chicago author-date
De Vlieghere, Elly, Koen Van de Vijver, Eva Blondeel, Nathan Carpentier, Rouba Ghobeira, Jarne Pauwels, Sebastian Riemann, et al. 2023. “A Preclinical Platform for Assessing Long-Term Drug Efficacy Exploiting Mechanically Tunable Scaffolds Colonized by a Three-Dimensional Tumor Microenvironment.” BIOMATERIALS RESEARCH 27 (1). https://doi.org/10.1186/s40824-023-00441-3.
Chicago author-date (all authors)
De Vlieghere, Elly, Koen Van de Vijver, Eva Blondeel, Nathan Carpentier, Rouba Ghobeira, Jarne Pauwels, Sebastian Riemann, Manon Minsart, Charlotte Fieuws, Johanna Mestach, Ans Baeyens, Nathalie De Geyter, Charlotte Debbaut, Hannelore Denys, Benedicte Descamps, Kathleen Claes, Anne Vral, Jo Van Dorpe, Kris Gevaert, Bruno De Geest, Wim Ceelen, Sandra Van Vlierberghe, and Olivier De Wever. 2023. “A Preclinical Platform for Assessing Long-Term Drug Efficacy Exploiting Mechanically Tunable Scaffolds Colonized by a Three-Dimensional Tumor Microenvironment.” BIOMATERIALS RESEARCH 27 (1). doi:10.1186/s40824-023-00441-3.
Vancouver
1.
De Vlieghere E, Van de Vijver K, Blondeel E, Carpentier N, Ghobeira R, Pauwels J, et al. A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment. BIOMATERIALS RESEARCH. 2023;27(1).
IEEE
[1]
E. De Vlieghere et al., “A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment,” BIOMATERIALS RESEARCH, vol. 27, no. 1, 2023.
@article{01HFE5YWPCTX2FQTSM36N7GKGG,
  abstract     = {{Background
Long-term drug evaluation heavily relies upon rodent models. Drug discovery methods to reduce animal models in oncology may include three-dimensional (3D) cellular systems that take into account tumor microenvironment (TME) cell types and biomechanical properties.

Methods
In this study we reconstructed a 3D tumor using an elastic polymer (acrylate-endcapped urethane-based poly(ethylene glycol) (AUPPEG)) with clinical relevant stiffness. Single cell suspensions from low-grade serous ovarian cancer (LGSOC) patient-derived early passage cultures of cancer cells and cancer-associated fibroblasts (CAF) embedded in a collagen gel were introduced to the AUPPEG scaffold. After self-organization in to a 3D tumor, this model was evaluated by a long-term (> 40 days) exposure to a drug combination of MEK and HSP90 inhibitors. The drug-response results from this long-term in vitro model are compared with drug responses in an orthotopic LGSOC xenograft mouse model.

Results
The in vitro 3D scaffold LGSOC model mimics the growth ratio and spatial organization of the LGSOC. The AUPPEG scaffold approach allows to test new targeted treatments and monitor long-term drug responses. The results correlate with those of the orthotopic LGSOC xenograft mouse model.

Conclusions
The mechanically-tunable scaffolds colonized by a three-dimensional LGSOC allow long-term drug evaluation and can be considered as a valid alternative to reduce, replace and refine animal models in drug discovery.}},
  articleno    = {{104}},
  author       = {{De Vlieghere, Elly and Van de Vijver, Koen and Blondeel, Eva and Carpentier, Nathan and Ghobeira, Rouba and Pauwels, Jarne and Riemann, Sebastian and Minsart, Manon and Fieuws, Charlotte and Mestach, Johanna and Baeyens, Ans and De Geyter, Nathalie and Debbaut, Charlotte and Denys, Hannelore and Descamps, Benedicte and Claes, Kathleen and Vral, Anne and Van Dorpe, Jo and Gevaert, Kris and De Geest, Bruno and Ceelen, Wim and Van Vlierberghe, Sandra and De Wever, Olivier}},
  issn         = {{1226-4601}},
  journal      = {{BIOMATERIALS RESEARCH}},
  keywords     = {{Biomedical Engineering,Biomaterials,Medicine (miscellaneous),Ceramics and Composites,Stiffness,Micro-environment,Pre-clinical,Drug evaluation,Long-term,3D cancer model}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{18}},
  title        = {{A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment}},
  url          = {{http://doi.org/10.1186/s40824-023-00441-3}},
  volume       = {{27}},
  year         = {{2023}},
}
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