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Development of cell therapy for hepatic failure due to dysfunction of hepatic parenchymal cells.

Research Project

Project/Area Number 09470273
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionNational Children's Medical Research Center

Principal Investigator

AMEMIYA Hiroshi  National Children's Medical Research Center, General Director, 小児医療研究センター, センター長 (80009563)

Co-Investigator(Kenkyū-buntansha) LI Xiao-kang  National Children's Medical Research Center, Researcher, 小児医療研究センター・実験外科生体工学部, 研究員 (60321890)
ENOSAWA Shin  National Children's Medical Research Center, Division head, 小児医療研究センター・実験外科生体工学部, 室長 (40232962)
SUZUKI Seiichi  National Children's Medical Research Center, Defector, 小児医療研究センター・実験外科生体工学部, 部長 (00111386)
OKUYAMA Torayuki  National Children's Medical Research Center, Division head, 小児医療研究センター・先天異常研究部, 室長 (40177192)
李 小康  国立小児病院, 小児医療研究センター・実験外科生体工学部, 科学技術庁特別研究員
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 1999: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1998: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1997: ¥4,100,000 (Direct Cost: ¥4,100,000)
Keywordshepatocyte / differentiation / amniotic epithelial cells / CrmA / apoptosis / rat / cell transplantation / cell therapy / 肝不全 / 遺伝子導入 / 肝細胞増殖 / 肝細胞分化 / 肝上皮幹細胞 / 免疫抑制
Research Abstract

Although there are various kinds of novel mdical technology at present, hepatic failure is one of serious diseases which have no fundamental therapies except for liver transplantation or only allopathy such as ultraviolet irradiation against hyperbilirubinemia etc, and some of the hepatic failure are due to congenital malfunction. In this research, we did basic investigation on hepatic cell therapy which may replace liver transplantation or innovate gene therapy. The main topics are 1) search off actor(s) or condition to develop or to maintain differentiated function of hepatocytes, 2) suitable cell types for hepatic cell transplantation, and 3) conditionhg of successful cell transplantation by gene transduction. We developed intra-gel culture of rat hepatocytes with rat fetus extract and rat plasma. This culture condition maintained drug metabolizing activity assessed by 7-ethoxycoumarin deethylation tip to for 7 days, as well as morphological feature of hepatocyte. For cell transplantation, we used amniotic epithelial cells from rat fetus. The certain population of the amniotic cells expressed albumin during culture period as was reported by human amniotic epithelial cells (J Hum Genet 45 171 2000). The cells can be stored frozen without marked impairment of viability. The cell division was 2.7 times at average and telomerase activity was detectable in the cells from feyses at early stage (day 14), suggesting that telomerase transfection may accelerate eell proliferation. To establish successful eell survival after transplantation, ants-apoptotic gene, CrmA, was transfected to hepatocytes, which showed long-term survival against rejection response.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Nakajima T,EnosawaS,et al.: "Cytological examination of rat amniotic epithelial cells and cell transplantation to the liver."Cell Transplantation. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li XK et al.: "Inhibition of Fas-mediated fulminant hepatitis in CrmA gene-transfected mice."Biochem Biophys Res Commun. 273(1). 101-109 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakuragawa N,Enosawa S,et al.: "Human amniotic epithelial cells are promising transgene carriers for allogeneic cell transplantation into liver."J Hum Genet. 45(3). 171-176 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tamura A et al.: "Immunosuppressive therapy using FTY720 combined with tacrolim us in rat liver transplantation."Surgery. 127(1). 47-54 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yata Y,Enosawa S,et al.: "An improved method for the purification of stellate calls from rat liver with Dichloromethylene Diphosphate(CL2MDP)."Methods in Cell Science. 21. 19-24 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokiwa T et al.: "SV40 large T antigen immortalization of rat hepatic stellate-like cells."In Vitro Cell Dev Biol-Animal. 35. 246-247 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li XK et al.: "Prolonged survival of rat liver allografts transfected with Fas ligand-expressing plasmid."Transplantation. 66(11). 1416-1423 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Enosawa S et al.: "Higher efficiency of retrovirus transduction in the late stage of primary culture of hepatocytes from nonteated than from partially hepatectomized rat."Cell Transplant. 7(4). 413-416 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 雨宮 浩、絵野沢 伸: "肝臓を標的とする再生医療の役割."バイオインダストリー. 17巻2号. 57-63 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakajima T, Enosawa S, Mitani T, Li X-K, Suzuki S, Amemiya H, Koiwai O, Sakuragawa N.: "Cytological examination of rat amniotic epithelial cells and cell transplantation to the liver."Cell Transplant. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li XK, Fujino M, Guo L, Okuyama T, Funeshima N, Hashimoto M, Okabe K, Yaginuma H, Mikoshiba K, Enosawa S, Amemiya H, Suzuki S.: "Inhibition of Fas-mediated fulminant hepatitis in CrmA gene-transfected mice."Biochem Biophys Res Commun.. 273(1). 101-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakuragawa N, Enosawa S, Ishii T, Thangavel R, Tashiro T, Okuyama T, Suzuki S.: "Human amniotic epithelial cells are promising transgene carriers for allogeneic cell transplantation into liver."J Hum Genet.. 45(3). 171-6 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yata Y, Enosawa S, Suzuki S, Li XK, Tamura A, Kimura H, Takahara T, Watanabe A.: "An improved method for the purification of stellate cells from rat liver with dichloromethylene diphosphate (CL2MDP)."Methods Cell Sci.. 21(1). 19-24 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tamura A, Li XK, Funeshima N, Enosawa S, Anemiya H, Kitajima M, Suzuki S.: "Immunosuppressive therapy using FTY720 combined with tacrolimus in rat liver transplantation."Surgery.. 127(1). 47-54 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokiwa T, Yata Y, Takahara T, Watanabe A, Enosawa S, Suzuki S, Kano J, Noguchi M.: "SV40 large T antigen immortalization of rat hepatic stellate-like cells."In Vitro Cell Dev Biol Anim.. 35(5). 246-7 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li XK, Okuyama T, Tamura A, Enosawa S, Kaneda Y, Takahara S, Funashima N, Yamada M, Amemiya H, Suzuki S.: "Prolonged survival of rat liver allografts transfected with Fas ligand-expressing Plasmid."Transplantation.. 66(11). 1416-23 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Enosawa S, Suzuki S, Li XK, Okuyama T, Fujino M, Amemiya H.: "Higher efficiency of retrovirus transduction in the late stage of primary culture of hepatocytes from nontreated than from partially hepatectomized rat."Cell Transplant.. 7(4). 413-6 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Amemiya H, Enosawa S.: "Role of liver regeneration to develop novel medical therapy.(in Japanese)"BIOINDUSTRY. 17(2). 57-63 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yata Y. et al.: "An improved method for the purification of stellate cells from rat liver with Dichloromethylene Diphosphate (CL2MDP)"Methods in Cell Science. 21. 19-24 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokiwa T. et al.: "SV40 large T antigen immortalization of rat hepatic stellate-like cells"In Vitro Cell Dev Biol-Animal. 35. 246-247 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujino M. et al.: "On/off switching Fas-ligand gene expression in liver by Cre/loxP adenovirus vector system"Transplant Proc. 31(1, 2). 753-754 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Enosawa S et al.: "Higher efficiency of retrovirus transduction in the late stage of primary culture of hepatocytes from non-treated than from partially hepatectomized rat." Cell Transplantation. 7(4). 413-416 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Li XK et al.: "Prolonged survival of rat liver allografts transfected with Fas-ligand expressing plasmid." Transplantation. 66(11). 1416-1423 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okuyama T et al.: "Fas-mediated apoptosis is involved in the elimination of gene-transducted hepatocytes with E1/E3-deleted adenoviral vectors." J Gastroent Hepatol. 13. 113-118 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okuyama T et al.: "Efficient Fas-ligand gene expression in rodent liver after intravenous injection of a recombinant adenovirus by the use of a Cre-mediated switching system." Gene Therapy. 5. 1047-1053 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Enosawa S et al.: "An attempt to add biological functions by genetic engineering in order to produce high-performance bioreactor cells for hybid artificial liver : Transfection of glutamine synthetase into chinese hamster ovary (CHO) cell." Cell Transplantation. 6. 537-540 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Enosawa S et al.: "Higher efficiency of retrovirus transduction in the late stage of primary culture of hepatocytes from non-treated than from partially hepatectomized rat." Cell Transplantation. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki S et al.: "The induction of lymphocyte apoptosis in MRL lpr/lpr mice treated with FTY720." Clin Exp Immunol. 107. 103-111 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki S et al.: "An immunosuppressive regimen using FTY720 combined with cyclosporine in kidney transplantation." Transplant Int. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Li X-K et al.: "FTY720,a novel immunosuppressive agent,enhances upregulation of the cell adhesion molecules ICAM-1 in TNF-a treated human umblical vein endothelial cells." Transplant Proc. 29. 1265-1266 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Li X-K et al.: "Induction of lymphocyte apoptosis by a novel immunosuppressant FTY720 : Relation with Fas,Bcl-2 and Bax expression." Transplant Proc. 29. 1267-1268 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Okuyama T et al.: "J Gastroent Hepat" Fas-mediated apoptosis is involved in the elimination of gene-transducted hepatocytes with E1/E3-deleted adenoviral vectors.(in press), (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Okuyama T et al.: "Human Gene Therapy" Efficient Fas-ligand gene expression in rodent liver after intravenous injection of a recombinant adenovirus by the use of a Cre-mediated switching system.(in press), (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2017-10-11  

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