The application of a murine bone bioreactor as a model of tumor: bone interaction

Clin Exp Metastasis. 2006;23(7-8):345-56. doi: 10.1007/s10585-006-9044-8. Epub 2006 Nov 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bioreactors*
  • Bone Development
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / physiology
  • Bone Neoplasms / secondary*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Durapatite
  • Female
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Tissue Engineering*
  • Transforming Growth Factor beta / physiology


  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Transforming Growth Factor beta
  • Durapatite