title: The application of a murine bone bioreactor as a model of tumor: bone interaction.
abstract: A limited number of in vivo models that rapidly assess bone development or allow for the study of tumor progression in a closed in vivo environment exist. To address this, we have used bone tissue engineering techniques to generate a murine in vivo bone bioreactor. The bioreactor was created by implanting an osteoconductive hydroxyapatite scaffold pre-loaded with saline as a control or with bone morphogenetic protein-2 (BMP-2) to the murine femoral artery. Control and BMP-2 bioreactors were harvested and histologically assessed for vascularization and bone formation at 6 and 12 weeks post implantation. BMP-2 significantly enhanced the formation of osteoid within the bioreactor in comparison to the controls. To test the in vivo bone bioreactor as a model of tumor: bone interaction, FVB mice were implanted with control or BMP-2 treated bioreactors. After 6 weeks, an osteolytic inducing mammary tumor cell line tagged with luciferase (PyMT-Luc) derived from the polyoma virus middle T (PyMT) model of mammary tumorigenesis was delivered to the bioreactor via the femoral artery. Analysis of luciferase expression over time demonstrated that the presence of osteoid in the BMP-2 treated bioreactors significantly enhanced the growth rate of the PyMT-Luc cells in comparison to the control group. These data present a unique in vivo model of ectopic bone formation that can be manipulated to address molecular questions that pertain to bone development and tumor progression in a bone environment.
authors.affiliation: Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, T-4323, Medical Center North, Nashville, TN 37232, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Halpern
authors.forename: Conor C
authors.initials: CC
authors.lastname: Lynch
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fleming
authors.forename: David
authors.initials: D
authors.lastname: Hamming
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Martin
authors.forename: Herbert S
authors.initials: HS
authors.lastname: Schwartz
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Matrisian
authors.forename: Ginger E
authors.initials: GE
authors.lastname: Holt
mesh_terms: D000818:Animals; D019149:Bioreactors; D001846:Bone Development; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D001859:Bone Neoplasms / Q000556:secondary*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D017886:Durapatite; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D017886:Durapatite