Engineering a humanized bone organ model in mice to study bone metastases

Martine, Laure C., Holzapfel, Boris M., McGovern, Jacqui A., Wagner, Ferdinand, Quent, Verena M., Hesami, Parisa, Wunner, Felix M., Vaquette, Cedryck, De-Juan-Pardo, Elena M., Brown, Toby D., Nowlan, Bianca, Wu, Dan Jing, Hutmacher, Cosmo Orlando, Moi, Davide, Oussenko, Tatiana, Piccinini, Elia, Zandstra, Peter W., Mazzieri, Roberta, Levesque, Jean-Pierre, Dalton, Paul D., Taubenberger, Anna V. and Hutmacher, Dietmar W. (2017) Engineering a humanized bone organ model in mice to study bone metastases. Nature Protocols, 12 4: 639-663. doi:10.1038/nprot.2017.002

Author Martine, Laure C.
Holzapfel, Boris M.
McGovern, Jacqui A.
Wagner, Ferdinand
Quent, Verena M.
Hesami, Parisa
Wunner, Felix M.
Vaquette, Cedryck
De-Juan-Pardo, Elena M.
Brown, Toby D.
Nowlan, Bianca
Wu, Dan Jing
Hutmacher, Cosmo Orlando
Moi, Davide
Oussenko, Tatiana
Piccinini, Elia
Zandstra, Peter W.
Mazzieri, Roberta
Levesque, Jean-Pierre
Dalton, Paul D.
Taubenberger, Anna V.
Hutmacher, Dietmar W.
Title Engineering a humanized bone organ model in mice to study bone metastases
Journal name Nature Protocols   Check publisher's open access policy
ISSN 1750-2799
Publication date 2017-04-01
Sub-type Article (original research)
DOI 10.1038/nprot.2017.002
Open Access Status Not yet assessed
Volume 12
Issue 4
Start page 639
End page 663
Total pages 25
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2018
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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School of Medicine Publications
UQ Diamantina Institute Publications
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