Human induced pluripotent stem cell-derived hepatic cell lines as a new model for host interaction with hepatitis B virus
Project/Area Number |
15K15285
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Gastroenterology
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Asahina Yasuhiro 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (00422692)
|
Co-Investigator(Kenkyū-buntansha) |
柿沼 晴 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座講師 (30372444)
|
Project Period (FY) |
2015-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | HBV / Human iPS cell / cccDNA / iPS細胞 / B型肝炎ウイルス / NTCP / 肝幹・前駆細胞 / 幹細胞分化 |
Outline of Final Research Achievements |
HBV is not eradicated by current antiviral therapies due to persistence of HBV cccDNA in host cells, and thus development of novel culture models for productive HBV infection is urgently needed, which will allow the study of HBV cccDNA eradication. To meet this need, we developed culture models of HBV infection using human induced pluripotent stem cell-derived hepatocyte lineages, including immature proliferating hepatic progenitor-like cell lines and differentiated hepatocyte-like cells. These cells were susceptible to HBV infection, produced HBV particles, and maintained innate immune responses. This study provides evidence that iPS-derived hepatic cell lines can be utilized for novel HBV culture models with genetic variation to investigate the interactions between HBV and host cells and the development of anti-HBV strategies.
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Report
(3 results)
Research Products
(38 results)
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[Journal Article] Hepatitis B Surface Antigen Reduction by Switching from Long-term Nucleoside/nucleotide Analog Administration to Pegylated Interferon.2017
Author(s)
Tamaki N, Kurosaki M, Kusakabe A, Orito E, Joko K, Kojima Y, Kimura H, Uchida Y, Hasebe C, Asahina Y, Izumi N.
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Journal Title
J Viral Hepat
Volume: 印刷中
Issue: 8
Pages: 672-678
DOI
Related Report
Peer Reviewed
-
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[Journal Article] ITPA gene variation and ribavirin-induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin.2017
Author(s)
Murakawa M, Asahina Y, Nagata H, Nakagawa M, Kakinuma S, Nitta S, Kawai-Kitahata F, Otani S, Kaneko S, Miyoshi M, Tsunoda T, Asano Y, Sato A, Itsui Y, Azuma S, Nouchi T, Furumoto Y, Asano T, Chuganji Y, Tohda S, Watanabe M.
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Journal Title
Hepatol Res
Volume: 印刷中
Issue: 11
Pages: 1212-1218
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Hepatic IFNL4 expression is associated with non-response to interferonbased therapy through the regulation of basal interferon-stimulated gene expression in chronic hepatitis C patients.2017
Author(s)
Murakawa M, Asahina Y, Kawai-Kitahata F, Nakagawa M, Nitta S, Otani S, Nagata H, Kaneko S, Asano Y, Tsunoda T, Miyoshi M, Itsui Y, Azuma S, Kakinuma S, Tanaka Y, Iijima S, Tsuchiya K, Izumi N, Tohda S, Watanabe M.
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Journal Title
J Med Virol
Volume: in press
Issue: 7
Pages: 1241-1247
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Complex pattern of resistance-associated substitutions of hepatitis C virus after daclatasvir/asunaprevir treatment failure.2017
Author(s)
Itakura J, Kurosaki M, Hasebe C, Osaki Y, Joko K, Yagisawa H, Sakita S, Okushin H, Satou T, Hisai H, Abe T, Tsuji K, Tamada T, Kobashi H, Mitsuda A, Ide Y, Ogawa C, Tsuruta S, Takaguchi K, Murakawa M, Asahina Y, Enomoto N, Izumi N.
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Journal Title
PLoS One
Volume: -
Issue: 10
Pages: e0165339-e0165339
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of resistance-associated NS5A mutations in hepatitis C virus on viral production and susceptibility to antiviral reagents.2016
Author(s)
Nitta S, Asahina Y, Matsuda M, Yamada N, Sugiyama R, Masaki T, Suzuki R, Kato N, Watanabe M, Wakita T, Kato T.
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 34652-34652
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Bone Morphogenetic Protein-4 Modulates Proliferation and Terminal Differentiation of Fetal Hepatic Stem/Progenitor Cells.2016
Author(s)
Goto F, Kakinuma S, Miyoshi M, Tsunoda T, Kaneko S, Sato A, Asano Y, Otani S, Azuma S, Nagata H, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Nakagawa M, Asahina Y, Watanabe M.
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Journal Title
Hepatol Res
Volume: 印刷中
Issue: 9
Pages: 941-952
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Irregular vascular pattern by contrast-enhanced ultrasonography and high serum Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level predict poor outcome after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma.2016
Author(s)
Takada H, Tsuchiya K, Yasui Y, Nakakuki N, Tamaki N, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Asahina Y, Enomoto N, Izumi N.
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Journal Title
Cancer Med
Volume: 5
Issue: 11
Pages: 3111-3120
DOI
Related Report
Peer Reviewed
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[Journal Article] Serial measurement of Wisteria floribunda agglutinin positive Mac-2-binding protein is useful for predicting liver fibrosis and the development of hepatocellular carcinoma in chronic hepatitis C patients treated with IFN-based and IFN-free therapy.2016
Author(s)
Nagata H, Nakagawa M, Nishimura-Sakurai Y, Asano Y, Tsunoda T, Miyoshi M, Kaneko S, Goto F, Otani S, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Seishin Azuma S, Kakinuma S, Tojo N, Tohda T, Asahina Y, Watanabe M, the Ochanomizu Liver Conference Study Group.
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Journal Title
Hepatol Int
Volume: 10
Issue: 6
Pages: 956-964
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Human induced pluripotent stem cell-derived hepatic cell line as a new model for host interaction with hepatitis B virus.2016
Author(s)
Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Miyoshi M, Tsunoda T, Nitta S, Asano Y, Nagata H, Otani S, Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Nakauchi H, Iwamoto M, Watashi K, Wakita T, Sugiyama M, Mizokami M, Shimotohno K, Watanabe M.
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 29358-29358
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Evaluation of IFN resistance in newly established genotype 1b HCV cell culture system.2016
Author(s)
Taniguchi M, Tasaka-Fujita M, Nakagawa M, Watanabe T, Kawai-Kitahata F, Otani S, Goto F, Nagata H, Kaneko S, Nitta S, Murakawa M, Nishimura-Sakurai Y, Azuma S, Itsui Y, Mori K, Yagi S, Kakinuma S, Asahina Y, Watanabe M.
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Journal Title
J Clin Transl Hepatol
Volume: 4
Issue: 1
Pages: 5-11
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Matrix Metalloproteinase-14 Mediates Formation of Bile Ducts and Hepatic Maturation of Fetal Hepatic Progenitor Cells.2016
Author(s)
Otani S, Kakinuma S, Kamiya A, Goto F, Kaneko S, Miyoshi M, Tsunoda T, Asano Y, Kawai-Kitahata F, Nitta S, Nakata T, Okamoto R, Itsui Y, Nakagawa M, Azuma S, Asahina Y, Yamaguchi T, Koshikawa N, Seiki M, Nakauchi H, Watanabe M.
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Journal Title
Biochem Biophys Res Commun
Volume: 469
Issue: 4
Pages: 1062-1068
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Comprehensive analyses of mutations and hepatitis B virus integration in hepatocellular carcinoma with clinicopathological features.2016
Author(s)
Kawai-Kitahata F, Asahina Y, Tanaka S, Kakinuma S, Murakawa M, Sayuri Nitta S, Watanabe T, Otani S, Taniguchi M, Goto F, Nagata H, Kaneko S, Tasaka-Fujita M, Nishimura-Sakurai Y, Azuma S, Itsui Y, Nakagawa M, Tanabe M, Takano S, Fukasawa M, Sakamoto M, Maekawa S, Enomoto N, Watanabe M.
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Journal Title
Journal of Gastroenterology
Volume: 51
Issue: 5
Pages: 473-486
DOI
Related Report
Peer Reviewed
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[Journal Article] Efficacy of additional radiofrequency ablation after transcatheter arterial chemoembolization for intermediate hepatocellular carcinoma.2016
Author(s)
Azuma S, Asahina Y, Nishimura-Sakurai Y, Kakinuma S, Kaneko S, Nagata H, Goto F, Ootani S, Kawai-Kitahata F, Taniguchi M, Murakawa M, Watanabe T, Tasaka-Fujita M, Itsui Y, Nakagawa M, Watanabe M.
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Journal Title
Heptol Res
Volume: 46
Issue: 4
Pages: 312-9
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] JSH Guidelines for the Management of Hepatitis C Virus Infection: A 2016 update for genotype 1 and 2.2016
Author(s)
Asahina Y, Izumi N, Hiromitsu K, Kurosaki M, Koike K, Suzuki F, Takikawa H, Tanaka A, Tanaka E, Tanaka Y, Tsubouchi H, Hayashi N, Hiramatsu N, Yotsuyanagi H
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Journal Title
Hepatol Res
Volume: 46
Issue: 2
Pages: 129-165
DOI
Related Report
Peer Reviewed
-
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[Journal Article] Genetic polymorphisms of IL28B and PNPLA3 are predictive for HCV related rapid fibrosis progression and identify patients who require urgent antiviral treatment with new regimens.2015
Author(s)
Tamaki N, Kurosaki M, Higuchi M, Takada T, Nakakuki N, Yasui Y, Suzuki S, Tsuchiya K, Nakanishi H, Itakura J, Takahashi Y, Ogawa S, Tanaka Y, Asahina Y, Izumi N
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Journal Title
PLoS One
Volume: 10
Issue: 9
Pages: e0137351-e0137351
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Amino acid polymorphisms in hepatitis C virus core affect infectious virus production and major histocompatibility complex class I molecule expression2015
Author(s)
Tasaka-Fujita M, Sugiyama N, Kang W, Masaki T, Murayama A, Yamada N, Sugiyama R, Tsukuda S, Watashi K, Asahina Y, Sakamoto N, Wakita T, Shin EC, Kato T
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Journal Title
Sci Rep
Volume: 5
Issue: 1
Pages: 13994-14002
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Reduced changes in bone mineral density in CHB patients receiving tenofovir alfenamide (TAF) compared with tenofovir disoproxil fumarate.2016
Author(s)
Seto WK, Asahina Y, Peng, Stanciu CYC, Abdurakhmanov D, Flaherty JF, Kim K, Gaggar A, Subramanian M, Tabak F, Tuan T. Nguyen TT, Chan HLT
Organizer
The 67th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2016).
Place of Presentation
Boston, USA
Year and Date
2016-11-11
Related Report
Int'l Joint Research / Invited
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[Presentation] Genetically modified human induced pluripotent stem cell-derived hepatic progenitor-like cell lines as a model for interaction between hepatitis В virus and host cells.2016
Author(s)
Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Miyoshi M, Tsunoda T, Nitta S, Sato A, Asano Y, Nagata H, Otani S, Kawai-Kitahata F, Murakawa M, Nakagawa M, Azuma S, Watanabe M.
Organizer
The 67th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2016).
Place of Presentation
Boston, USA
Year and Date
2016-11-11
Related Report
Invited
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[Presentation] A model for interaction between HBV and host cells derived from human induced pluripotent stem cells.2016
Author(s)
Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Nitta S, Tsunoda T, Miyoshi M, Asano Y, Nagata H, Goto F, Otani S, Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma AS, Watanabe M.
Organizer
The 51th annual meeting of the European association for the study of the liver (EASL The International Liver Congress 2016)
Place of Presentation
Barcelona, Spain
Year and Date
2016-04-13
Related Report
Invited
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[Presentation] A model for interaction between HBV and host cells derived from human induced pluripotent stem cells.2016
Author(s)
Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Nitta S, Tsunoda T, Miyoshi M, Asano Y, Nagata H, Goto F, Otani S, Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Watanabe M
Organizer
The 51th annual meeting of the European association for the study of the liver (EASL The International Liver Congress 2016)
Place of Presentation
Barcelona(Spain)
Year and Date
2016-04-13
Related Report
Int'l Joint Research
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[Presentation] Comprehensive analyses of mutations and hepatitis B virus integration in hepatocellular carcinoma.2016
Author(s)
Kawai-Kitahata F, Asahina Y, Tanaka S, Kakinuma S, Murakawa M, Nitta S, Otani S, Goto F, Nagata H, Kaneko S, Asano Y, Miyoshi M, Tsunoda T, Azuma S, Itsui Y, Nakagawa M, Tanabe M, Maekawa S, Enomoto N, Watanabe M
Organizer
25th conference of the Asian Pacific Association for the Study of the Liver (APASL 2016)
Place of Presentation
グランドプリンスホテル新高輪(東京都港区)
Year and Date
2016-02-20
Related Report
Int'l Joint Research
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[Presentation] A model for interaction between HBV and host cells derived from human induced pluripotent stem cells.2016
Author(s)
Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Nitta S, Tsunoda T, Miyoshi M, Asano Y, Nagata H, Goto F, Otani S, Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Watanabe M.
Organizer
25th conference of the Asian Pacific Association for the Study of the Liver (APASL 2016)
Place of Presentation
グランドプリンスホテル新高輪(東京都港区)
Year and Date
2016-02-20
Related Report
Int'l Joint Research
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[Presentation] Human induce pluripotent stem cell-dereived hepatic progenitor-like cells and hepatocyte-like cells as a model for interaction between hepatitis B virus and host cells.2015
Author(s)
Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Nitta S, Tsunoda T, Miyosi M, Nagata H, Goto F, Otani S, Murakawa M, Kawai-Kitahata F, Itsui Y, Nakagawa M, Azuma S, Watanabe M
Organizer
The 66th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2015)
Place of Presentation
San Francisco(USA)
Year and Date
2015-11-13
Related Report
Int'l Joint Research
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[Presentation] Comprehensive analyses of mutations and hepatitis B virus integration in hepatocellular carcinoma with clinicopathological features.2015
Author(s)
Kawai-Kitahata F, Asahina Y, Tanaka S, Kakinuma S, Murakawa M, Nitta S, Watanabe T, Otani S, Goto F, Nagata H, Kaneko S, Azuma S, Itsui Y, Nakagawa M, Tanabe M, Maekawa S, Enomoto N, Watanabe M
Organizer
The 66th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2015)
Place of Presentation
San Francisco(USA)
Year and Date
2015-11-13
Related Report
Int'l Joint Research
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[Presentation] Expression of IFN lambda 4 in liver is closely associated with non-response to antiviral therapy through the regulation of basal expression of ISGs in chronic hepatitis C patients but not in hepatitis B.2015
Author(s)
Murakawa M, Asahina Y, Kawai-Kitahata F, Nagata H, Kaneko S, Nitta S, Watanabe T, Itsui Y, Nakagawa M, Kakinuma S, Iijima S, Tanaka Y, Watanabe M, Tanaka Y
Organizer
The 66th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2015)
Place of Presentation
San Francisco(USA)
Year and Date
2015-11-13
Related Report
Int'l Joint Research
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[Presentation] Serial change of resistant associated variants during early phase of NS3/4A triple therapy and the final virological outcome: analyses by ultra-deep sequenceing technology.2015
Author(s)
Watanabe T, Asahina Y, Nakagawa M, Kakinuma S, Itsui Y, Nagata H, Murakawa M, Kawai-Kitahata F, Miura M, Maekawa S, Enomoto N, Watanabe M
Organizer
The 66th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2015)
Place of Presentation
San Francisco(USA)
Year and Date
2015-11-13
Related Report
Int'l Joint Research
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