Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells

Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder. Patients with LFS are predisposed to a various type of tumors, including osteosarcoma--one of the most frequent primary non-hematologic malignancies in the childhood and adolescence. Therefore, LFS provides an ideal mode...

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Bibliographic Details
Published in:Journal of visualized experiments 2018-06 (136)
Main Authors: Zhou, Ruoji, Xu, An, Tu, Jian, Liu, Mo, Gingold, Julian A, Zhao, Ruiying, Lee, Dung-Fang
Format: Article
Language:English
Subjects:
Adolescent
Cancer Research
Cell Differentiation
Humans
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
Li-Fraumeni Syndrome - genetics
Li-Fraumeni Syndrome - metabolism
Male
Mesenchymal Stem Cells - metabolism
Osteosarcoma - diagnosis
Osteosarcoma - pathology
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Summary:Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder. Patients with LFS are predisposed to a various type of tumors, including osteosarcoma--one of the most frequent primary non-hematologic malignancies in the childhood and adolescence. Therefore, LFS provides an ideal model to study this malignancy. Taking advantage of iPSC methodologies, LFS-associated osteosarcoma can be successfully modeled by differentiating LFS patient iPSCs to mesenchymal stem cells (MSCs), and then to osteoblasts--the cells of origin for osteosarcomas. These LFS osteoblasts recapitulate oncogenic properties of osteosarcoma, providing an attractive model system for delineating the pathogenesis of osteosarcoma. This manuscript demonstrates a protocol for the generation of iPSCs from LFS patient fibroblasts, differentiation of iPSCs to MSCs, differentiation of MSCs to osteoblasts, and in vivo tumorigenesis using LFS osteoblasts. This iPSC disease model can be extended to identify potential biomarkers or therapeutic targets for LFS-associated osteosarcoma.
ISSN:1940-087X
1940-087X
DOI:10.3791/57664