2022 Fiscal Year Final Research Report
Generation of human iPSC-derived liver buds resistant to hepatitis B virus infection
Project/Area Number |
20K08952
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
|
Research Institution | The University of Tokyo |
Principal Investigator |
Ueno Yasuharu 東京大学, 医科学研究所, 特任助教 (60375235)
|
Co-Investigator(Kenkyū-buntansha) |
谷口 英樹 東京大学, 医科学研究所, 教授 (70292555)
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Keywords | B型肝炎ウイルス / ヒトiPS細胞 / ゲノム編集 / 肝臓オルガノイド / HBV感染 |
Outline of Final Research Achievements |
In this study, in order to create human liver tissues resistant to hepatitis B virus (HBV) infection, we investigated the generation of hepatocytes and liver organoids lacking the HBV infection receptor by genome editing of human iPS cells. In human iPS cells, NTCP, a candidate factor for HBV infection receptor, was knocked out, and hepatocytes and liver organoids were induced to evaluate resistance to HBV infection. human iPS cells lacking NTCP had the ability to differentiate into hepatocytes, and hepatocytes lacking NTCP showed resistance to infection with HBV. NTCP-deficient hepatocytes were resistant to HBV infection. Furthermore, we demonstrated that liver organoids can be generated from NTCP-deficient human iPS cells and that NTCP-deficient human liver organoids are resistant to infection against HBV. In conclusion, we have established a basic technology for generating liver tissue resistant to HBV infection using human iPS cells.
|
Free Research Field |
細胞生物学
|
Academic Significance and Societal Importance of the Research Achievements |
HBVはヒト肝細胞に選択的に感染し、核内で安定的な微小環状ゲノム(cccDNA)に変換される他、一部は宿主細胞のゲノム内に組み込まれる。 これまでにHBV感染細胞からcccDNAを排除する手法等が検討されてきたが、未だ有効な手法は確立されていない。本研究では、新規アプローチによるHBVの新規治療法開発に向け、肝臓の再生医療への応用が期待されているヒトiPS細胞由来肝臓オルガノイドにHBV感染耐性を付与するための手法の検討を実施した。ヒトiPS細胞を用いてHBVに感染耐性を示す肝臓組織を創出するための基盤技術が確立されたことにより、新たなB型肝炎治療法の研究開発の加速が期待される。
|