Martine, Laure C. and Holzapfel, Boris M. and McGovern, Jacqui A. and Wagner, Ferdinand and Quent, Verena M. and Hesami, Parisa and Wunner, Felix M. and Vaquette, Cedryck and De-Juan-Pardo, Elena M. and Brown, Toby D. and Nowlan, Bianca and Wu, Dan Jing and Hutmacher, Cosmo Orlando and Moi, Davide and Oussenko, Tatiana and Piccinini, Elia and Zandstra, Peter W. and Mazzieri, Roberta and Levesque, Jean-Pierre and Dalton, Paul D. and Taubenberger, Anna V. and Hutmacher, Dietmar W. (2017) Engineering a humanized bone organ model in mice to study bone metastases. NATURE PROTOCOLS, 12 (4). pp. 639-663. ISSN 1754-2189, 1750-2799
Full text not available from this repository. (Request a copy)Abstract
Current in vivo models for investigating human primary bone tumors and cancer metastasis to the bone rely on the injection of human cancer cells into the mouse skeleton. This approach does not mimic species-specific mechanisms occurring in human diseases and may preclude successful clinical translation. We have developed a protocol to engineer humanized bone within immunodeficient hosts, which can be adapted to study the interactions between human cancer cells and a humanized bone microenvironment in vivo. A researcher trained in the principles of tissue engineering will be able to execute the protocol and yield study results within 4-6 months. Additive biomanufactured scaffolds seeded and cultured with human bone-forming cells are implanted ectopically in combination with osteogenic factors into mice to generate a physiological bone 'organ', which is partially humanized. The model comprises human bone cells and secreted extracellular matrix (ECM); however, other components of the engineered tissue, such as the vasculature, are of murine origin. The model can be further humanized through the engraftment of human hematopoietic stem cells (HSCs) that can lead to human hematopoiesis within the murine host. The humanized organ bone model has been well characterized and validated and allows dissection of some of the mechanisms of the bone metastatic processes in prostate and breast cancer.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MESENCHYMAL STEM-CELLS; PROSTATE-CANCER METASTASIS; HUMAN BREAST-CANCER; IN-VIVO MODEL; HUMAN HEMATOPOIETIC NICHE; MOUSE MODELS; MARROW-CELLS; HUMAN TUMOR; TISSUE; SCAFFOLDS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:00 |
| Last Modified: | 25 Feb 2019 10:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/181 |
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