期刊
BONE
卷 158, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2021.116018
关键词
Bone; Tumour; Osteosarcoma; Ultrastructure; Collagen; Animal model; Orthotopic bone model; Tissue humanisation; Humanised animal model; Rat model
资金
- National Health and Medical Research Council of Australia [1082313]
- Australian Research Council [ARC ITCC 160100026]
- German Research Association (DFG) [CI 203/2-1]
- Humboldt Postdoctoral Fellowship
- IHBI Innovation Ideas Grant from QUT
- Advance Queensland Women's Research Assistance Program [WRAP035-2019RD1]
An orthotopic humanised tissue-engineered osteosarcoma model in a genetically engineered rat has been successfully developed, allowing for the study of metastatic spread to the lung. The results highlight the crucial role of humanised animal models in bone disease research.
Current xenograft animal models fail to accurately replicate the complexity of human bone disease. To gain translatable and clinically valuable data from animal models, new in vivo models need to be developed that mimic pivotal aspects of human bone physiology as well as its diseased state. Above all, an advanced bone disease model should promote the development of new treatment strategies and facilitate the conduction of common clinical interventional procedures. Here we describe the development and characterisation of an orthotopic humanised tissue-engineered osteosarcoma (OS) model in a recently genetically engineered x-linked severe combined immunodeficient (X-SCID) rat. For the first time in a genetically modified rat, our results show the successful implementation of an orthotopic humanised tissue-engineered bone niche supporting the growth of a human OS cell line including its metastatic spread to the lung. Moreover, we studied the inter-and intraspecies differences in ultrastructural composition of bone and calcified tissue produced by the tumour, pointing to the crucial role of humanised animal models.
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