Related Experiment Video
Updated: Jul 13, 2025
3D Microtissues for Injectable Regenerative Therapy and High-throughput Drug Screening
Published on: October 4, 2017
A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a
Elly De Vlieghere1,2,3, Koen Van de Vijver3,4, Eva Blondeel1,3
1Department of Human Structure and Repair, Laboratory of Experimental Cancer Research, Ghent University, Ghent, Belgium.
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.
