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Nat Protoc. 2017 Apr;12(4):639-663. doi: 10.1038/nprot.2017.002. Epub 2017 Mar 2.

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

Author information

1
Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
2
Orthopedic Center for Musculoskeletal Research, University of Wuerzburg, Wuerzburg, Germany.
3
Department of Orthopedics for the University of Regensburg, Asklepios Klinikum Bad Abbach, Bad Abbach, Germany.
4
Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany.
5
Department of Obstetrics and Gynecology, Martin-Luther-Krankenhaus, Academic Teaching Hospital of the Charité Berlin, Berlin, Germany.
6
The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
7
Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
8
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
9
Stem Cell Biology Group - Blood and Bone Diseases Program, Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
10
Faculty of Medicine and Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
11
Department of Functional Materials in Medicine and Dentistry, and Bavarian Polymer Institute, University of Wuerzburg, Wuerzburg, Germany.
12
Biotec TU Dresden, Dresden, Germany.
13
George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
14
Institute for Advanced Study, Technical University Munich, Garching, Germany.

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.

PMID:
28253234
DOI:
10.1038/nprot.2017.002
[Indexed for MEDLINE]

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