Engineering a humanized bone organ model in mice to study bone metastases.
Nat Protoc. 2017 Apr;12(4):639-663
Authors: Martine LC, Holzapfel BM, McGovern JA, Wagner F, Quent VM, Hesami P, Wunner FM, Vaquette C, De-Juan-Pardo EM, Brown TD, Nowlan B, Wu DJ, Hutmacher CO, Moi D, Oussenko T, Piccinini E, Zandstra PW, Mazzieri R, Lévesque JP, Dalton PD, Taubenberger AV, Hutmacher DW
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 [PubMed - indexed for MEDLINE]