Tissue-engineered bone tumor as a reproducible human in vitro model for studies of anti-cancer drugs

We investigated changes in bone and Ewing's Sarcoma transcriptomes among control and treated cells grown in 2D plates, or within engineered bone scaffolds. Overall design: This study was made up of 2 main tiers of testing—in tier 1, TE-Bone (Scaffold with human osteoblasts) and TE-Tumor (human osteoblasts and Ewing's sarcoma aggregates) scaffolds were exposed to Linsitinib (3 week treatment, 12uM), Doxorubicin (2 week treatment, 4.16uM), or vehicle controls. Treatments were carried out in 1 week cycles with 3 days of drug treatment, followed by 4 days of rest period. In the second tier of testing, TE-Tumor scaffolds were treated with vehicle, cisplatin (3, 10, or 30uM), dexamethasone (0.1, 1, or 10uM), methotrexate (0.1, 1, or 10uM), vincristine (0.1, 1, or 10uM), or MAP (cisplatin, doxorubicin and methotrexate mixture) at a high or low concentration. Scaffolds were treated over 2 one week cycles, followed by a 2 week recovery period with no drug treatment. In addition to the studies with the tissue engineered scaffolds, Ewings sarcoma cells were grown in 2D (96-well plate) as a comparator, and treated on the same regimens.