Development of a bone tumor model under in vitro conditions

Kömez, Aylin
Osteosarcoma is one of the most common types of primary bone cancerous tumor. The structure of this tumor is solid, hard and irregular. Three dimensional (3D) models mimicking tumor tissue are needed for screening efficacy of the anticancer drugs for an effective personalized therapy. This study describes the design and production of a 3D bone tumor model (BTM) by using tissue engineering approach, and shows its capability to assess the efficacy of an anticancer drug. The model consists of two parts: (1) poly(lactic acid-co-glycolic acid) (PLGA)/beta-tricalcium phosphate (β-TCP) scaffold seeded with human fetal osteoblastic cells (hFOB) and human umbilical vein endothelial cells (HUVECs) (serve as the healthy microenvironment around the bone tumor tissue), and (2) collagen sponge seeded with human osteosarcoma cells (Saos-2) (mimic the tumor tissue). The second part is inserted in the central cavity of PLGA/β-TCP scaffold to form 3D BTM. Responsiveness of the developed model to anticancer drug, doxorubicin, was studied as an indicator of mimicking of bone tumor. Confocal micrographs on day 21 of incubation present migration of HUVEC cells to the tumor region. Increase in expression of angiogenic factors (VEGF, bFGF, and IL-8) in the tumor component also confirms cell migration. Doxorubicin demonstrated high efficacy when applied to the BTM model, and resulted in a 7-fold decrease in viability and apoptosis of Saos-2 cells (measured by caspase-3 enzyme activity). These show the suitability of the model in screening drug efficacies for personalized treatments.


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Citation Formats
A. Kömez, “Development of a bone tumor model under in vitro conditions,” Ph.D. - Doctoral Program, Middle East Technical University, 2019.