2020 Fiscal Year Final Research Report
Establishment of an artificial osteosarcoma stem cell line by transduction of defined factors with with iPS cell technology
Project/Area Number |
18K09031
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56020:Orthopedics-related
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Research Institution | Kobe University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
原 仁美 神戸大学, 医学部附属病院, 助教 (40437489)
深瀬 直政 神戸大学, 医学部附属病院, 医員 (60579324)
秋末 敏宏 神戸大学, 保健学研究科, 教授 (90379363)
青井 貴之 神戸大学, 科学技術イノベーション研究科, 教授 (00546997)
川上 洋平 神戸大学, 医学研究科, 医学研究員 (50626570)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Keywords | 骨肉腫 / がん幹細胞 / iPS細胞 |
Outline of Final Research Achievements |
This study aimed to generate the cancer stem cell (CSC)-like cells from human osteosarcoma cells by introducing reprogramming factors, and to reveal the obtained cell characteristics. We could obtain the osteosarcoma stem cells by transduction of OCT3/4-KLF4-SOX2 genes into a human osteosarcoma cell line MG63. mRNA expression of reported CSC markers significantly increased in the cells. In the cells, WST-8 assays revealed that significantly lower cell proliferation and higher chemo-resistance were observed. After osteogenic induction, strongly positive staining of Alizarin red S and ALP was also observed. In vivo experiments, tumors from the cells were significantly larger in size, and strong immunopositivity of Ki-67, Osteocalcin and HIF1-α was observed. We could generate the osteosarcoma stem cells by introducing reprogramming factors. This method could be useful to elucidate the molecular mechanisms and the effective therapeutic targets in human osteosarcoma.
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Free Research Field |
骨軟部悪性腫瘍
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Academic Significance and Societal Importance of the Research Achievements |
本研究は,希少かつ治療困難な骨肉腫において,iPS細胞作製に用いられる技術を応用することで骨肉腫幹細胞を得ることに成功した初めての研究である.この成功によって骨肉腫においてもがん幹細胞研究を遂行することが可能となる革新的な成果であり,学術的意義が非常に高い.また得られた細胞の特性を解析することは,骨肉腫における幹細胞の機能を解明することに繋がり,骨肉腫の新たな病態理解や治療標的分子の同定とそれらに基づく新規治療開発を行うことが期待出来る。とくに新規治療開発は限られた治療法しか存在しない骨肉腫の臨床において,非常に有用な成果であり,社会的意義も非常に高いものである.
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