| Project/Area Number |
18KK0461
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Miki Kenji 京都大学, iPS細胞研究所, 研究員 (10772759)
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| Project Period (FY) |
2018 – 2020
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
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| Keywords | 脱細胞化マトリックス / 3Dプリンター / ヒトiPS細胞 / 心筋細胞 / 心外膜細胞 / 心内膜細胞 / バイオプリンター / 3D心筋組織 / iPS細胞 / HCM |
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| Outline of Final Research Achievements |
In this study, I established differentiation methods to obtain highly pure human iPSC-derived cardiomyocytes, epicardial cells and endocardial cells. I injected and perfused them in a decellularized heart tissue and cultured them, and obtained beating heart tissues by naked eyes. Furthermore, I also showed that cardiomyocytes in the decellularized heart had more mature sarcomeres and mitochondria than cardiomyocytes in two-dimensional culture.
In additioon, I succeeded in constructing a three-layered heart tissue that can be perfused using a 3D bioprinter and hydrogel. This tissue did not undergo necrosis in the center of the tissue even after one month of culture. In the cardiomyocytes of this tissue, sarcomere and mitochondria maturation was also confirmed to be better than that of cardiomyocytes cultured in two-dimensional culture.
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| Academic Significance and Societal Importance of the Research Achievements |
脱細胞化マトリックスを用いることにより、血管網が存在する拍動する心臓組織の構築に成功し、この研究は今後の心臓としてのポンプ機能をより詳細に解析できることになり、将来的な臓器創生・移植/創薬への応用・病態解明などに貢献できると考えている。3Dプリンターを用いた灌流可能な心筋組織に関しては、より長期間組織内の細胞を生存させることが可能となり、特に創薬や薬剤試験などへの応用が期待できる。これら高度な三次元心臓モデルを構築することで、臓器創出やPrecision Medicineの実現は医学分野の発展だけでなく、工学、情報科学分野の発展、更に医療費の抑制といった医療経済にも貢献しうる可能性がある。
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