ヒトの原始肝細胞の長期的機能維持 in vitro

Chengang Xiang¹, Yuanyuan Du¹, Gaofan Meng¹

¹School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.

Science (New York, N.Y.)

|April 27, 2019

まとめ

初期ヒト肝細胞 (PHHs) の維持は,実験室内では困難である. 新しい化学カクテル (5C) は,薬剤スクリーニングのためのB型肝炎ウイルス (HBV) 感染をサポートする長期的なPHH培養を可能にします.

科学分野:

ヘパトロジー
細胞生物学
ウイルス学

背景:

末期分化細胞,特に肝細胞は,in vitroで維持することが難しい.
既存の方法では,肝細胞の機能や特性を長期間維持することができないことが多い.

研究の目的:

主要なヒト肝細胞 (PHHs) の長期維持のための方法を開発する.
B型肝炎ウイルス (HBV) 感染を研究し,抗ウイルス薬の開発のための堅牢なインビトロモデルを確立する.

主な方法:

5つの化学物質 (5C) の組み合わせを用いた細胞信号伝達経路の調節
5C化学カクテルでPHHを培養する.
PHH遺伝子発現プロファイルと肝細胞特有の機能の評価
5C培養のPHHのHBV感染と4週間のモニタリング

主要な成果:

5Cアプローチを用いてPHHsの長期維持を in vitroで達成した.
5C培養のPHHは,新鮮に分離された肝細胞に似た遺伝子発現と機能を示した.
ウイルス粒子の生成とccDNA形成を含む,HBV感染の完全なサイクルを in vitroで成功裏に再現した.
培養されたPHHで最大4週間持続したHBV感染が実証された.

結論:

化学的アプローチ (5C) は,ヒトの原始肝細胞の機能をin vitroで効果的に維持する.
この方法は,長期 HBV 感染の研究のための安定したプラットフォームを提供します.
開発されたシステムは,HBV細胞生物学と抗ウイルス薬のスクリーニングに適しています.

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