2019 Fiscal Year Final Research Report
Human miniature artificial liver for drug verification
Project/Area Number |
19K21341
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Project/Area Number (Other) |
18H06246 (2018)
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund (2019) Single-year Grants (2018) |
Review Section |
0905:Surgery of the organs maintaining homeostasis and related fields
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Research Institution | Kumamoto University |
Principal Investigator |
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Project Period (FY) |
2018-08-24 – 2020-03-31
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Keywords | ミニチュアヒト人工肝臓 / 薬剤 ex-vivoスクリーニングツール / 脱細胞鋳型肝臓 / ヒト初代培養肝細胞 |
Outline of Final Research Achievements |
Creation of artificial organs contributes to the field of drug development for cancers. Here, we aimed to create a miniature human artificial liver in which rat decellularized liver was replaced with human primary hepatocytes, and to evaluate its potential as a drug ex-vivo screening tool. The liver was excised from 6-8 week-old Wistar rats, and the decellularized liver in which the medium was replaced was prepared. This liver was incorporated into a closed artificial liver screening circuit. An artificial nose was incorporated into the circuit as an oxygen enrichment device. Furthermore, in order to recellularize decellularized liver, we developed a protocol to efficiently obtain primary hepatocytes from human excised liver. In the future, we plan to replace the decellularized liver of the developed screening kit with human primary hepatocytes and evaluate liver damage by adding some drugs candidates for development.
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Free Research Field |
消化器外科、肝臓外科、トランスレーショナルリサーチ
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Academic Significance and Societal Importance of the Research Achievements |
薬剤は肝臓で代謝されることが多い。新規薬剤の開発においては、有効性とともに安全性についても十分な検討が必要である。現在、基礎的な動物実験で安全性を確認することが多いが、ヒト細胞での検討ではないためより安全性の確認を行うためにはヒト細胞の使用が望ましい。今回我々の行った研究により、新規薬剤スクリーニングキットしてのヒトミニチュア肝臓の開発が進んだことにより、将来、治験を行う前に、解剖学的立体構造を有した状態でのヒト肝細胞を用いた安全性の確認を行うことができるようになる可能性がある。
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