| Project/Area Number |
16H01850
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Kyushu University |
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Principal Investigator |
Suzuki Atsushi 九州大学, 生体防御医学研究所, 教授 (30415195)
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| Research Collaborator |
Horisawa Kenichi
Maehara Yoshihiko
Shirabe Ken
Kumamaru Wataru
Ohkawa Yasuyuki
Takashima Yasuo
Yamamoto Junpei
Miura Shizuka
Udono Miyako
Kawamata Masaki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000)
Fiscal Year 2018: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2017: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2016: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
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| Keywords | 肝臓 / 細胞分化 / ダイレクトリプログラミング / 再生 / がん / 細胞・組織 / 発生・分化 / 再生医学 / 移植・再生医療 / 遺伝子 |
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| Outline of Final Research Achievements |
In our previous study, we succeeded in direct reprogramming of mouse fibroblasts into hepatocyte-like cells using a set of defined transcription factors (TFs). These induced hepatocyte-like (iHep) cells have hepatocyte-specific properties in vitro and in vivo. However, the hepatic functions of iHep cells were insufficient compared with those of primary hepatocytes. Thus, in this study, we sought to induce functional differentiation of iHep cells, and found that cell-aggregate formation can rapidly induce hepatic maturation of iHep cells through activation of Hippo signaling. Thus, iHep cell aggregates may provide insights into potential therapies for liver diseases. Moreover, we also found that combinatorial transduction of three TFs stably suppressed cancer-specific phenotypes of hepatocellular carcinoma (HCC) cells and induced the expression of hepatocyte marker genes. Thus, it is suggested that direct reprogramming technology can develop to an effective therapeutic strategy for HCC.
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| Academic Significance and Societal Importance of the Research Achievements |
iHep細胞の機能的成熟誘導法の開発やその分子機構の解明は、iHep細胞を用いた肝疾患患者に対する新しい移植医療の実現や、個人レベルで薬剤の効果や毒性を評価できる次世代型検査システムの構築に大きく貢献すると考えられる。また、本研究において肝細胞へのダイレクトリプログラミング技術ががん治療に応用可能なことが実証されたことから、ダイレクトリプログラミング技術を利用した肝がん細胞の肝細胞化が、肝がんの治療や制御を担う新しい治療法として発展することが期待される。
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