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

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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.

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Acknowledgements

This work was supported by NIH grant CA103079 (LMM and HSS) and by the Susan G. Komen Foundation grant PDF02–1394 (CCL).

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Authors and Affiliations

  1. Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, T-4323, Medical Center North, Nashville, TN, 37232, USA

    Jennifer Halpern, Conor C. Lynch, David Hamming, Herbert S. Schwartz & Ginger E. Holt

  2. Department of Cancer Biology, Vanderbilt University, Nashville, TN, 37232, USA

    Conor C. Lynch, Jonathan Fleming, Michelle D. Martin & Lynn M. Matrisian

Authors
  1. Jennifer Halpern
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  2. Conor C. Lynch
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  3. Jonathan Fleming
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  4. David Hamming
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  5. Michelle D. Martin
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  6. Herbert S. Schwartz
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  7. Lynn M. Matrisian
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  8. Ginger E. Holt
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Correspondence to Ginger E. Holt.

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Authors Jennifer Halpern and Conor C. Lynch contributed equally to this work.

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Halpern, J., Lynch, C.C., Fleming, J. et al. The application of a murine bone bioreactor as a model of tumor: bone interaction. Clin Exp Metastasis 23, 345–356 (2006). https://doi.org/10.1007/s10585-006-9044-8

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  • DOI: https://doi.org/10.1007/s10585-006-9044-8

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