Developing a 3D bone model of osteosarcoma to investigate cancer mechanisms and evaluate treatments

Abstract

Osteosarcoma is the most common primary bone cancer, occurring frequently in children and young adults. Patients are treated with surgery and multi-agent chemotherapy, and despite the introduction of mifamurtide in 2011, there has been little improvement in survival for decades. 3-dimensional models offer the potential to understand the complexity of the osteosarcoma tumor microenvironment and aid in developing new treatment approaches. An osteosarcoma 3D bone core model was developed using human trabecular bone and the chorioallantoic membrane (CAM), to form a functioning vasculature. A tri-culture of cells, stromal cells, macrophages, and the Saos-2 osteosarcoma cell line, were implanted into this model to simulate components of the tumor microenvironment, and mifamurtide was tested in this context. Immunohistochemistry and micro-CT were performed to assess phenotypic and structural effects of implantation. Successful integration and angiogenesis of the bone cores were observed after incubation on the CAM. The 3D bone model also showed similar characteristics to osteosarcoma patient samples including CD68 and CD105 expression. Incubating bone cores with mifamurtide induced a reduction of cellular markers and an increase in bone volume. This 3D bone core model has the potential to investigate osteosarcoma tumor microenvironment and provides a representative model for evaluation of novel therapies.

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Identifiers

ORCID for Stephen A. Beers: orcid.org/0000-0002-3765-3342

ORCID for Janos M. Kanczler: orcid.org/0000-0001-7249-0414

ORCID for Juliet C. Gray: orcid.org/0000-0002-5652-4722

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