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Transdifferentiation of bone marrow-derived cells into hepatic lineage cells: the methods of transdifferentiation in vitro and hepatic cells transplantation in vivo

Research Project

Project/Area Number 14570467
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOSAKA UNIVERSITY

Principal Investigator

KISO Shinichi  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40335352)

Co-Investigator(Kenkyū-buntansha) FUKUI Kouji  Osaka University Graduate School of Medicine, Medical Staff, 医学部附属病院, 医員(臨床研究)
IGURA Takumi  Osaka University Graduate School of Medicine, Medical Staff, 医学部附属病院, 医員(臨床研究)
TAMURA Shinji  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30243223)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsBone marrow cells / hepatocytes / trans-differentiation / bFGF / HGF / 再生医療 / 肝幹細胞 / 増殖因子 / 肝前駆細胞 / 分化誘導
Research Abstract

Evidence that bone marrow cells have trans-differencing potential to hepatocytes have been described in recent reports. However, the molecular mechanism underlying this phenomenon is unclear. To address this issue, we investigated the parameters involved in the trans-differentiation ob bone marrow cells into hepatic lineage. (Methods) Mouse BM cells were cultured in a collagen gel without or with growth factors, including basic fibroblast growth factor. The expression of hepatocyte-specific markers, cholangiocyte-specific marker and liver-enriched transcription factors was identified by RT-PCR and immunohistochemistry. (Results) Basic fibroblast growth factor was found to be the most effective for inducing albumin in cultured BM cells. Furthermore, on stimulation of basic fibroblast growth factor, BM cells were found to express other hepatocyte-specific markers and a cholangiocyte-specific marker. This conversion was found to be associated with the induction of transcription factors including hepatocyte nuclear factors and GATA family proteins. (Conclusion) We established an in vitro culture system in which mouse bone marrow cells could trans-differentiate to hepatic lineage cells in response to growth factors. In particular, basic fibroblast growth factor has the ability to induce the trans-differentiation into hepatic lineage cells from BM cells.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Shinichi Kiso(1番目), Shinji Tamura(3番目), (他13名): "Liver Regenaration in Heparin-Binding EGF-like Growth Factor Transgenic Mice after Partial Hepatectomy."Gastroenterology. 124. 701-707 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Kamada, S.Tamura(2番目), S.Kiso(3番目), K.Fukui(7番目), (他12名): "Enhanced carbon tetrachroride-induced liver fibrosis in mice lacking adiponectin."Gastroenterology. 125. 1796-1807 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Sawai, S.Tamura(2番目), K.Fukui(3番目), S.Kiso(8番目), (他5名): "Expression of ephrin-B1 in hepatocellular carcinoma : possible involvement in neovascularization"J Hepatology. 39. 991-996 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shigeru Sakuda, Shinji Tamura(2番目), Shinichi Kiso(6番目), (他8名): "NF-κB activation in non-parenchymal liver cells after partial hepatectomy in rats : possible involvement in expression of heparin-binding epidermal growth lactor-like growth factor."J Hepatology. 36. 527-533 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shigeru Sakuda, Shiji Tamura(2番目), Shinichi Kiso(6番目), (他10名): "Activation of signal transducer and activator transcription 3 nd expression of suppressor of cytokine signal 1 during liver regeneration in rats."J Hepatology. 36. 378-384 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ayuko Saeki, Shinji Tamura(2番目), Shinichi Kiso(4番目), (他4名): "Frequent impairment of the spindle assembly checkpoint in the hepatocellular carcinoma."Cancer. 94. 2047-2054 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinichi Kiso, Sumio Kawata, Shinji Tarnura, Yoshiaki Inul, Yuichi Yoshida, Yoshiyuki Sawai, Shinobu Umeki, Nobuyuki Ito, Akira Yamada, Jun-ichiro Miyagawa, Shigeki Higashiyama, Takao Iwawaki, Michiko Saito, Naoyuki Taniguchi, Yuji Matsuzawa, Kenji Kohno.: "Liver Regeneration in Heparin-Binding EGF-like Growth Factor Transgenic Mice after Partial Hepatectomy."Gastroenterology. 124. 701-707 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshihiro Kamada, Shinji Tamura, Shinichi Kiso, Hitoshi Matsumoto, Yukiko Saji, Yuichi Yoshida, Koji Fukui, Norikazu Maeda, Hitoshi Nishizawa, Hiroyuki Nagaretanl, Yoshihiro Okamoto, Shinji Kihara, Jun-ichiro Miyagawa, Yasuhisa Shinomura, Tohru Funahashi, Yuji Matauzawa: "Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin."Gastroenterology. 125. 196-1807 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshiyuki Sawai, Shinji Tamura, Kouji Fukui, Nobuyuki Ito, Kazuho Imanaka, Ayuko Saeki, Shigeru Sakuda, Shinichi Kiso, YuJi Matsuzawa.: "Expression of ephrin-B1 in hepatocellular carcinoma : possible involvement In neovascularization."J Hepatology. 39. 991-996 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yashihiro Kamada, Shinji Tamura, Shinichi Kiso, Koji Fukui, Yoshinori Doi, Nobuyuki Ito, Yuki Terui, Takafumi Saito, Hisayoshi Watanabe, Hitoshi Togashi, Sumio Kawata, Yuji Matsuzawa: "Anglotensin II stimulates the nuclear translocation of Smad2 and induces PAl-1 mRNA In rat hepatic stellate cells."Hepatology Research. 25. 296-305 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shigeru Sakuda, Shinji Tamura, Akira Yamada, Jun-ichiro Miyagawa, Koji Yamamoto, Shinichi Kiso, Nobuyuki Ito, Shigeki Higashiyama, Naoyuki Taniguchi, Sumio Kawata, Yuji Matsuzawa.: "NF-kB activation in non-parenchymal liver cells after partial hepatectomy in rats: possible involvement in expression of heparin-binding epidermal growth factor-like growth factor."J Hepatology. 36. 527-533 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shigeru Sakuda, Shiji Tamura, Akira Yamada, Jun-ichiro Miyagawa, Koji Yamamoto, Shinichi Kiso, Nobuyuki Ito, Kazuho Imanaka, Akira Wada, Tetsuji Naka, Tadamitsu Kishimoto, Sumio Kawata, Yuji Matsuzawa.: "Activation of signal transducer and activator transcription 3 nd expression of suppressor of cytokine signal 1 during liver regeneration in rats."J Hepatology. 36. 378-384 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ayuko Saeki, Shinji Tamura, Nobuyuki Ito, Shinichi Kiso, Yasuo Matsuda, Iwao Yambuuchi, Sumio Kawata, Yuji Matsuzawa.: "Frequent impairment of the spindle assembly checkpoint in the hepatocellular carcinoma."Cancer. 94. 2047-2054 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinichi Kiso(1番目), Shinji Tamura(3番目), 他13名: "Liver Regenaration in Heparin-Binding EGF-like Growth Factror Transgenic Mice after Partial Hepatectomy"Gastroenterology. 124. 701-707 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Kamada, S.Tamura(2番目), S.Kiso(3番目), K.Fukui(7番目), 他12名: "Enhanced carbon tetrachroride-induced liver fibrosis in mice lacking adiponectin"Gastroenterology. 125. 1796-1807 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Sawai, S.Tamura(2番目), K.Fukui(3番目), S.Kiso(8番目), 他5名: "Expression of ephrin-B1 in hepatocellular carcinoma : possible involvement in neovascularization"J Hepatology. 39. 991-996 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shigeru Sakuda, Shinji Tamura(2番目), Shinichi Kiso(6番目), 他8名: "NF-kB activation in non-parenchymal liver cells after partial hepatectomy in rats : possible involvement in expression of heparin-binding epidermal growth factor-like growth factor"J Hepatology. 36. 527-533 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shigeru Sakuda, Shinji Tamura(2番目), Shinichi Kiso(6番目), 他10名: "Activation of signal transducer and activator transcription 3 nd expression of suppressor of cytokine signal 1 during liver regeneration in rats"J Hepatology. 36. 378-384 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ayuko Saeki, Shinji Tamura(2番目), Shinichi Kiso(4番目), 他4名: "Frequent impairment of the spindle assembly checkpoint in the hepatocellular carcinoma"Cancer. 94. 2047-2054 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinichi Kiso(1番目), Shinjl Tamura(3番目), 他14名: "Liver Regeneration in Heparin-Binding EGF-like Growth Factror Transgenic Mice after Partial Hepatectomy"Gastroenterology. 124. 701-707 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshihiro Kamada, Shinji, Tamura(2番目), Shinichi Kiso(3番目), Koji Fukui(4番目), 他8名: "Angiotensin II stimulates the nuclear translocation of Smad2 and inducesPAI-1 mRNA in rat hepatic stellate cells"Hepatology Research. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shigeru Sakuda, Shinj Tamura(2番目), Shinichi Kiso(5番目), 他7名: "NF-kB activation in non-parenchymal liverr cells after partial hepatectomy in rats : possible involvement in expression of heparin-binding epidermal growth factor-like growth factor"J Hepatology. 36. 527-533 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shigeru Sakuda, Shiji Tamura(2番目), Shinichi Kiso(6番目), 他10名: "Activation of signal transducer and activator transcription 3 and expression of suppressor of cytokine signal 1 during liver regeneration in rats"J Hepatology. 36. 378-384 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ayuko Saeki, Shinji Tamura(2番目), Shinichi Kiso(4番目), 他5名: "Frequent impairment of the spindle assembly checkpoint in hepatocellular carcinoma"Cancer. 94. 2047-2054 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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