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Establishment of cell transplantation therapy for Wilson's disease using hepatic stem cells.

Research Project

Project/Area Number 13670781
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionAkita University

Principal Investigator

TERADA Kunihiko  Akita University School of Medicine, Associate Professor, 医学部, 助教授 (60197796)

Co-Investigator(Kenkyū-buntansha) KAMEDA Takashi  Akita University School of Medicine, Research Associate, 医学部, 助手 (00301119)
SUGIYAMA Toshihiro  Akita University School of Medicine, Professor, 医学部, 教授 (00127242)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsHepatic stem cell / Albumin / Collagen / Analbuminemic rat / Cell transplantation / Metabolic liver disease / Liver epithelial cell / Cell differentiation / 肝臓幹細胞 / α-フェトプロエイン / コラーゲンゲル / コラーゲンスポンジ / 肝星細胞
Research Abstract

[Aim]In this study, we aimed the establishment of cell transplantation therapy for metabolic liver diseases using hepatic stem cells, previously isolated from a rat liver. To this end, we examined function of the transplanted hepatic stem cells into liver whether cell transplantation was effective to treat metabolic liver diseases including Wilson's disease.
[Achievements](1) We have established a liver epithelia cell line, designated hepatic stem like (HSL) cell, from nonparenchymal fraction of healthy rat liver. (2) The HSL cells are small with 20μm in diameter and showed high nucleus/cytoplasm ratios. These cells expressed α-fetoprotein, but not albumin nor cytokeratin 19, indicating the cells have immature phenotype. (3) We cultured the HSL cells in collagen gels cr with hepatic stellate cells to investigate their potential to differentiate. Consequently, both of culture conditions induced the HSL cells to express albumin, showing that the HSL cells are able to differentiate into mature cells. (4) Finally, we examined whether the HSL cells will be able to manifest hepatic function in vivo after transplantation. To this end, we transplanted the HSL cells that were mixed with collagen gel or embedded in collagen sponge into analbuminemic rats. As a result, analbuminemic rats that showed the increased levels of serum albumin were 67% in the rats transplanted the HSL cells with collagen gel and 57% in the rats with collagen sponge. In those rats, the levels of serum albumin increased ten weeks after transplantation and maintained until 25 weeks after transplantation. These results suggest that the HSL cells are potential to differentiate and that the transplanted HSL cells differentiated into albumin producing cells and function as hepatocytes in vivo. The present study implies the possibility of clinical application of HSL cells for metabolic liver diseases.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (55 results)

All Other

All Publications (55 results)

  • [Publications] Kameda T et al.: "Anaysis of the celluar heterogeneity in the basal layer of mouse ear epidermis: an approach from partial decomposition in vitro and retroviral cell marking in vivo"Exp. Cell Res.. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyashita H, et al.: "Expression of copper-transporting P-type adenosine tri-phosphatasea (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin"Oral Oncol.. 39. 157-162 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oubu M, et al.: "Copper-transporting P-Type adenosine triphosphatase ATP7B is expressed in human gastric carcinoma"Cancer Lett.. 189. 33-38 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagai H, et al.: "Differentiation of liver epithelial (stem-like) cells into hepatocytes induced by coculture with hepatic stellate cells"Biochem. Biophys. Res. Commun.. 293. 1420-1425 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameda T, et al.: "Targeted elimination of the follicular label-retaining cells by photo-induced cell killing caused a defect on follicular renewal on mice"Genes Cells. 7. 923-931 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 寺田邦彦: "未分化肝臓由来細胞を利用した胆管癌の発生過程の解明"成人病と生活習慣病. 32. 1346-1347 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 杉山俊博, 他: "再生医学-肝臓幹細胞を用いたミニ肝臓の作製"秋田県医師会雑誌. 53. 1-7 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] KanzakiA, et al.: "Copper-transporting P-Type Adenosine Triphosphatase (ATP7B) Is Expressed in Human Breast Carcinoma"Jpn. J. Cancer Res.. 93. 70-77 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameda T, et al.: "Acceleration of the formation of cultured epithelium using the sonic hedgehog expressing feeder cells"Tissue Eng.. 7. 545-555 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harada M, et al.: "A Mutation of Wilson's Disease Protein, ATP7B, Is Degraded in the Proteasomes and Forms Protein Aggregates"Gastroenterology. 120. 967-974 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Demitsu T, et al.: "Hypertrichosis induced by latanoprost"J. Am. Acad. Dermatol.. 44. 721-723 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ichihara T, et al.: "Resistance to fluminant hepatitis and carcinogenesis conferred by overexpression of retinoblastoma protein in mouse liver"Hepatology. 33. 948-955 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 寺田邦彦, 他: "肝幹細胞を利用した肝組織の再構成"医学のあゆみ. 196. 383-386 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 寺田邦彦, 他: "幹細胞を用いたミニ肝臓の形成"GI Research. 93. 70-77 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 寺田邦彦, 他: "幹細胞を用いたミニ肝臓の形成"Molecular Medicine. 38. 16-22 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 寺田邦彦, 他: "肝臓幹細胞とその分化"肝臓. 42. 389-397 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terada K, et al.: "Intracellular copper transport and ATP7B, the Wilson's disease protein"Handbook of copper pharmacology and toxicology (Massaro E.J., ed.) (Humana Press, New Jersey.). 608 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama T, at al.: "Reconstitution of hepatic tissue using liver stem cells"Growth, proliferation, and apoptosis in hepatocytes (Okita K., ed.) (Springer-Verlag, Tokyo). 100 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 寺田邦彦, 他: "組織工学的手法を利用したミニ肝臓の作製"消化器疾患の最新医療(森岡恭彦、他編)(先端医療技術研究所. 東京). 663 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 寺田邦彦, 他: "肝幹細胞と毛幹細胞"化学フロンテイア(3)再生医工学(筏義人、編).(化学同人. 京都). 254 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameda T, et al.: "Analysis of the cellular heterogeneity in the basal layer of mouse ear epidermis: an approach from partial decomposition in vitro and retroviral cell marking in vivo"Exp. Cell Res., in press.. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyashita H, et al.: "Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin"Oral Oncol.. 39. 157-162 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oubu M, et al.: "Copper-transporting P-Type adenosine triphosphatase (ATP7B) is expressed in human gastric carcinoma"Cancer Lett.. 189. 33-38 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagai H, at al.: "Differentiation of liver epithelial (stem-like) cells into hepatocytes induced by coculture with hepatic stellate cells"Biochem. Biophys. Res. Commun.. 293. 1420-1425 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameda T, et al.: "Targeted elimination of the follicular label-retaining cells by photo-induced cell killing caused a defect on follicular renewal on mice"Genes Cells. 7. 923-931 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terada K.: "Analysis of biliary carcinogenesis using immature hepatic cells"J. Adult Dis.. 32. 1346-1347 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama T, et al.: "Regeneration medicine -Construction of mini liver using hepatic stem cells-"Akita Med. J.. 53. 1-7 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanzaki A, et al.: "Copper-transporting P-type adenosine triphosphatase (ATP7B) is expressed in human breast carcinoma"Jpn. J. Cancer Res.. 93. 70-77 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameda T, et al.: "Acceleration of the formation of cultured epithelium using the sonic hedgehog expressing feeder cells"Tissue Eng.. 7. 545-555 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harada M, et al.: "A mutation of Wilson's disease protein, ATP7B, is degraded in the proteasomes and forms protein aggregates"Gastroenterology. 120. 967-974 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Demitsu T, et al.: "Hypertrichosis induced by latanoprost"J. Am. Acad. Dermatol.. 44. 721-723 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ichihara T, et al.: "Resistance to fluminant hepatitis and carcinogenesis conferred by overexpression of retinoblastoma protein in mouse liver"Hepatology. 33. 948-955 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terada K, et al.: "Reconstitution of hepatic tissue using hepatic stem cells"IGAKU NO AYUMI. 196. 383-386 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terada K, et al.: "Construction of mini-liver using hepatic stem cells"GI Research. 93. 70-77 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terada K, et al.: "Construction of mini-liver using hepatic stem cells"Molecular Medicine. 38. 16-22 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terada K, at al.: "Hepatic stem cell and its differentiation"Acta Hepatologica Japonica. 42. 389-397 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terada K, et al.: "Intracellular copper transport and ATP7B, the Wilson's disease protein"Handbook of copper pharmacology and toxicology (Massaro E. J., ed.), Humana Press, New Jersey. 608 pages (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama T, et al.: "Reconstitution of hepatic tissue using liver stem cells"Growth, proliferation, and apoptosis in hepatocyles (Okita K., ed.), Springer-Verlag, Tokyo. 100 pages (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terada K, et al.: "Hepatic stem cell"Annual review of digestive disease in 2002 (Toda G., et al., eds.), Chuugai Igakusha, Tokyo. 34-39 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terada K, et al.: "Construction of mini-liver by tissue engineering techniques"Advanced Medicine for Digestive Diseases (Morioka Y., et al., eds.), Institute of Advanced Medical Techniques, Tokyo. 663 pages (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terada K, et al.: "Hepatic stem cell and hair stem cell"KAGAKU Frontier 3, Regenerative Medical Technology (Ikada Y., ed.), KAGAKU DOJIN, Kyoto. 254 pages (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameda T., et al.: "Analysis of the cellular heterogeneity in the basal layer of mouse ear epidermis : an approach from partial decomposition in vitro and retroviral cell marking in vivo"Exp.Cell Res.. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyashita H., et al.: "Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin"Oral Oncol.. 39・2. 157-162 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oubu M., et al.: "Copper-transporting P-Type adenosine triphosphatase (ATP7B) is expressed in human gastric carcinoma"Cancer Lett.. 189・1. 33-38 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagai H., et al.: "Differentiation of liver epithelial (stem-like) cells into hepatocytes induced by coculture with hepatic stellate cells"Biochem.Biophys.Res.Commun.. 293・5. 1420-1425 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kemeda T., et al.: "Targeted elimination of the follicular label-retaining cells by photo-induced cell killing caused a defect on follicular renewal on mice"Genes Cells. 7・9. 923-931 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 寺田邦彦: "未分化肝臓由来細胞を利用した胆管癌の発生過程の解明"成人病と生活習慣病. 32・10. 1346-1347 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Terada K., et al.: "Intracellular copper transport and ATP7B, the Wilson's disease protein, in "Handbook of copper pharmacology and toxicology""Massaro E.J., ed., Humana Press, New Jersey. 608 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 寺田邦彦, 他: "肝幹細胞"Annual Review 消化器 2002. 34-39 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanzaki A, et al.: "Copper-transporting P-Type Adenosine Triphosphatase (ATP7B) Is Expressed in Human Breast Carcinoma"Jpn. J. Cancer Res.. 93・1. 70-77 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kameda T, et al.: "Acceleration of the formation of cultured epithelium using the sonic hedgehog expressing feeder cells"Tissue Eng.. 7・5. 545-555 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Harada M, et al.: "A Mutation of Wilson's Disease Protein, ATP7B, Is Degraded in the Proteasomes and Forms Protein Aggregates"Gastroenterology. 120・4. 967-974 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 寺田邦彦, 他: "肝臓幹細胞とその分化"肝臓. 42・8. 389-397 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 寺田邦彦, 他: "肝幹細胞を利用した肝組織の再構成"医学のあゆみ. 196・5. 383-386 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugiyama T, et al.: "Reconstitution of hepatic tissue using liver stem cells"Growth, proliferation, and apoptosis in hepatocytes(Okita K., ed.), Springer-Verlag, Tokyo. 100 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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