Mechanisms of the osteoblast-like phenotypic conversion and its application to regenerative therapy of bone diseases
| Project/Area Number |
17H04316
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Mazda Osam 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00271164)
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| Co-Investigator(Kenkyū-buntansha) |
菅波 晃子 千葉大学, 大学院医学研究院, 助教 (10527922)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | ダイレクト・リプログラミング / 骨芽細胞 / 再生医学 / ダイレクト・コンヴァージョン / 再生医療 |
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| Outline of Final Research Achievements |
Recently we established procedures to directly convert human fibroblasts into osteoblasts by transducing some transcription factor genes or by treating the cells with a chemical compound. To apply this technology to bone regenerative therapy, it should be important to determine optimal procedures of the reprogramming, to understand the mechanisms of reprogramming, and to create 3D bone tissue in culture that is suitable for tailor-made autologous transplantation. In this project we explored chemical compounds that inhibit the molecules involved in the direct reprogramming by means of AI-based combinatorial chemistry. We also developed 3D bone tissue in culture using the directly converted osteoblasts. The results offered valuable information to apply the direct reprogramming technology to bone regenerative medicine in the near future.
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| Academic Significance and Societal Importance of the Research Achievements |
骨粗鬆症性骨折後の癒合不全などに対して骨再生医療が求められている。我々のダイレクト・リプログラミング法を用いれば、患者から極めて低侵襲に採取できる線維芽細胞から、高機能な移植用自家骨芽細胞を均質かつ無尽蔵に作出することができる。さらに、遺伝子導入が不要で化合物添加だけで誘導できること、効率が高く骨基質の産生能が高いこと、３Dスキャフォールド中で誘導することにより患者の病変部に合致した任意の形状にテーラーメイドで立体造形できることが必要とされる。本研究はこのような骨再生医療に適したケミカル・ダイレクト・リプログラミング技術につながる成果をもたらしたので、高い学術的および社会的意義を有する。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Treadmill Running Ameliorates Destruction of Articular Cartilage and Subchondral Bone, Not Only Synovitis, in a Rheumatoid Arthritis Rat Model.2018
Author(s)
Shimomura S, Inoue H, Arai Y, Nakagawa S, Fujii Y, Kishida T, Ichimaru S, Tsuchida S, Shirai T, Ikoma K, Mazda O, Kubo T.
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Journal Title
Int J Mol Sci
Volume: 19
Issue: 6
Pages: 1653-1653
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Nanogel tectonic porous 3D scaffold for direct reprogramming fibroblasts into osteoblasts and bone regeneration.2018
Author(s)
Sato Y, Yamamoto K, Horiguchi S, Tahara Y, Nakai K, Kotani SI, Oseko F, Pezzotti G, Yamamoto T, Kishida T, Kanamura N, Akiyoshi K, Mazda O.
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Journal Title
Sci Rep
Volume: 8
Issue: 1
Pages: 15824-15824
DOI
Related Report
Peer Reviewed / Open Access
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