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Induction of insulin secreting cell and its application for transplantation

Research Project

Project/Area Number 14370346
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionTohoku University

Principal Investigator

SUNAMURA Makoto  Tohoku University, Hospital, Lecturer, 病院, 講師 (10201584)

Co-Investigator(Kenkyū-buntansha) MIYAZAKI Jyunichi  Osaka University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (10200156)
HAMADA Hirofumi  Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (00189614)
EGAWA Shinichi  Tohoku University, Hospital, Research Associate, 病院・助手 (00270679)
FUKUYAMA Shoji  Tohoku University, Hospital, Research Associate, 病院・助手 (10344673)
MATSUNO Seiki  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80004737)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥11,800,000 (Direct Cost: ¥11,800,000)
Keywordspancreatic ductal epithelium / insulin secreting cell / pancreatic islet regeneration / PDX-1 gene / microarray analysis / 膵管上皮細胞 / ラ島 / PDX1 / マイクロアレイ / 膵ラ島 / VEGF / angiopoietin / 血管新生 / PDX-1 / 膵再生
Research Abstract

Islet transplantation has been expected to be effective therapy for insulin dependent DM (IDDM). However, this strategy is not established as a standard treatment for IDDM yet. The control of immuno-rejection is an obstacle for islet transplantation as same as the shortage of donors. The aim of this study is to develop the islet transplantation by using regeneration islet.
1.The induction of insulin secreting cells from human pancreatic duct cell (HPDC)
1)We established the HPDC cell line by the transfection of early expression gene of papilloma virus.
2)The change of shape of this HPDC was observed after the stimulation of extra cellular matrix of tissue culture.
3)We constructed the adenovirus vector for the transfection of PDX-1 gene. After transfection of PDX-1 gene into HPDC, the more expression of glucagon was detected than that of insulin. The cells made a mass looking like islet after in vitro culture. These HPDC became neoplastic tumor in vivo transplantation in mice.
2.The analysis of genes expression using microarray and the detection of genes relating to islet development
1)The mRNA was extracted from HPDC showing the insulin expression and used for DNA microarray study. The exspression of insulin was detected and genes showing the same pattern as insulin were selected.
2)The collaborate group has established insulin secreting cell from mouse embryonic stem cell (ISSC). We harvested the cells from 5 stage of this development and analyzed the mRNA expression using microarray system. The analysis of changes in gene expression revealed that the expression of genes relating to insulin was increased step by step. Theses results indicate that the responsible gene would be detected by the further study.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (10 results)

All 2006 2003 2002 Other

All Journal Article (6 results) Publications (4 results)

  • [Journal Article] Effect of tar-to-mouse bio-artificial pancreas xenotransplantation on diabetic renal damage and survival.2006

    • Author(s)
      Sakata N, Sunamura M. et al.
    • Journal Title

      Pancreas (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of rat-to-mouse bio-artificial pancreas xenotransplantation on diabetic renal damage and survival.2006

    • Author(s)
      Sakata N, Sunamura M, et al.
    • Journal Title

      Pancreas (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 安全な移植技術の開発をめざして2003

    • Author(s)
      磯部光章, 砂村眞琴, 他
    • Journal Title

      移植 38・4

      Pages: 263-277

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development of safe technical procedure for transplantation.2003

    • Author(s)
      Isobe M, Sunamura M, et al.
    • Journal Title

      Transplantation 38

      Pages: 263-277

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 膵ラ島移植における拒絶反応と再生医療の応用2002

    • Author(s)
      砂村眞琴, 松野正紀, 他
    • Journal Title

      日本アフェレシス学会誌 21・2

      Pages: 132-140

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Control of immuno-rejection for islet transplantation and the application of regeneration medicine.2002

    • Author(s)
      Sunamura M, Matsuno S, et al.
    • Journal Title

      Journal of Japanese Society of Apheresis 21,2

      Pages: 132-140

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] 砂村眞琴, 松野正紀: "膵ラ島移植における拒絶反応の制御と再生医療の応用"日本アフェレシス学会誌. 21・2. 132-140 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 砂村眞琴, 松野正紀: "膵内分泌細胞の再生-現状と展望"外科治療. 86・1. 15-20 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Duda D.G., Sunamura M 他: "Overexpression of the p53-inducible brain angiogenesis inhibitor 1 suppresses efficiently tumor angiogenesis"British Journal of Cancer. 86・3. 490-496 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hoshida T., Sunamura M 他: "Gene Therapy for pancreatic cancer using an adenovirus vector encoding soluble flt-1 vascular endothelial growth factor receptor"Pancreas. 25・2. 111-121 (2002)

    • Related Report
      2002 Annual Research Report

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

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