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Development of islet regeneration therapy by stem cell biology

Research Project

Project/Area Number 13854020
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionInstitute for Frontier Medical Sciences, Kyoto University

Principal Investigator

SUMI Shoichiro (2003)  Shiga university of medical science, Institute for Frontier Medical Sciences, Ass. Professor, 再生医科学研究所, 助教授 (80252906)

井上 一知 (2001-2002)  京都大学, 再生医科学研究所, 教授 (90168435)

Co-Investigator(Kenkyū-buntansha) TABATA Yasuhiko  Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (50211371)
MIYAZAKI Junichi  Osaka University, Department of Medicine, Professor, 医学部, 教授 (10200156)
中辻 憲夫  京都大学, 再生医科学研究所, 教授 (80237312)
角 昭一郎  京都大学, 再生医科学研究所, 助教授 (80252906)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥70,070,000 (Direct Cost: ¥53,900,000、Indirect Cost: ¥16,170,000)
Fiscal Year 2003: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2002: ¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2001: ¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000)
Keywordsembryonic stem cell / bio-artificial pancreas / immunoisolation / Langerhans islet (pancreatic islet) / subcutaneous transplantation / neovascularization / diabetes mellitus / induction of differentiation / 幹細胞 / ES細胞 / 膵島様細胞塊 / 塩基性線維芽細胞増殖因子 / インスリン産生細胞
Research Abstract

On the induction of differentiation toward insulin-producing cells, we successfully induced islet-like cell clusters (ICCs) form mouse embryonic stem cells by our own method. We showed that the ICCs contain electron microscopy-proved insulin granules, express pancrease-specific genes and reduce blood glucose levels of diabetic mice by transplantation.
On the development of bio-artificial pancreas of possible clinical subcutaneous transplantation, we established rod-type device to normalize hyperglycemia of diabetic mice using rat islets and porcine pancreatic endocrine cells as bioreactor and anti-complement polymer as immunoisolation membrane when transplanted into prevascularized subcutaneous site. In addition, we developed a novel method to make macroencapsulated islets using polyvinyl alcohol hydrogel as semipermeable membrane by freezing/thawing method. This method is much easier in sealing islets in the gel and suitable for making larger devices in comparison to our and reported previous methods.
On the methods to induce neovascularization for islet transplantation, we showed that gelatin microbeads impregnated with basic fibroblast growth factor in cooperation with collagen sponge has an excellent ability of vascular induction for islet transplantation in subcutaneous site. We further studied improved methods in ischemic rat skin flap models and newly developed rat leg model of prolonged ischemia.
From these results, we consider that the system of subcutaneously implantable bio-artificial pancreas has been established at least for mouse diabetic models. On this basis, we are now ready to develop larger bio-artificial pancreas devices for preclinical examination in diabetic larger animals including dogs.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Kawakami Y, Iwata H, Gu Y, Miyamoto M, Murakami Y, Balamurugan AN, Imamura M, Inoue K.: "Successful subcutaneous pancreatic islet transplantation using angiogenic growth factor releasing device."Pancreas. 23. 375-378 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang WJ, Gu Y, Tabata Y, Miyamoto M, Hori H, Nagata N, Toma M, Balamurugan AN, Kawakami Y, Nozawa M, Inoue K.: "Reversal of diabetes in mice by xenotransplantation of bioartificial pancreas in a prevascularized subcutaneous site."Transplantation. 73. 122-129 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang WJ, Gu Y, Hori H, Sakurai T, Hiura A, Sumi S, Inoue K.: "Subcutaneous transplantation of macroencapsulated porcine pancreatic endocrine cells normalizes hyperglycemia in diabetic mice."Transplantation. 76. 290-296 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim DH, Ishii M, Fujimiya M, Qi MG, Nakamura N, Yoshikawa T, Sumi S, Inoue K.: "In vivo functioning and transplantable mature pancreatic islet-like cell clusters differentiated from embryonic stem cell."Pancreas. 27. e34-e41 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Qi MG, Gu Y, Sakata N, Kjm DH, Shirouzu Y, Yamamoto C, Hiura A, Sumi S, Inoue K.: "PVA hydrogel sheet macroencapsulation for the bioartificial pancreas."Biomaterials. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawakami Y, Iwata H, Gu Y, Miyamoto M, Murakami Y, Balamurugan AN, Imamura M, moue K: "Successful subcutaneous pancreatic islet transplantation using angiogenic growth factor releasing device."Pancreas. 23. 375-378 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Xu, BY, Iwata H, Gu Y, Balamurugan AN, Murakami Y, Cui WX, Imamura M, moue K: "Functional comparison of the agarose microbeads and the developed three layer agarose microbeads as the bioartificial pancreas : An in, vitro study."Cell Transplant. 10. 403-408 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Xu BY, Gu YJ, Miyamoto M, Balamurugan AN, Cui WX, Imamura M, Iwata H, Inoue K: "The influence of anticomplement synthetic sulfonic polymers on function of pancreatic islets: an in vitro study."Cell Transplant. 10. 413-418 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gu Y, Tabata Y, Kawakami Y, Balamurugan AN, Hori H, Nagata N, Satake A: "Cui WX, Qi M, Misawa Y, Toma M, Miyamoto M, Nozawa M, moue K. Development of a new method to induce angiogenesis at subcutaneous site of strepotozotocin-induced diabetic rats for islet transplantation."Cell Transplant. 10. 453-457 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang WJ, Gu Y, Miyamoto M, Hori H, Nagata N, Balamurugan AN, Inoue K: "Effect of basic fibroblast growth factor on insulin secretion from micro-encapsulated pancreatic islets; An in vitro study."Cell Transplant. 10. 465-471 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang WJ,.Gu Y, Tabata Y, Miyamoto M, Hori H, Nagata N, Toma M, Balamurugan AN, Kawakami Y, Nozawa M, Inoue K: "Reversal of diabetes in mice by xenotransplantation of bioartificial pancreas in a prevascularized subcutaneous site."Transplantation. 73. 122-129 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang WJ, Gu Y, Hori H, Sakurai T, Hiura A, Sumi S, Inoue K: "Subcutaneous transplantation of macroencapsulated porcine pancreatic endocrine cells normalizes hyperglycemia in diabetic mice."Transplantation. 76. 290-296 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim DH, Ishii M, Fujimiya M, Qi MG, Nakamura N, Yoshikawa T, Sumi S, Inoue K: "In vivo functioning and transplantable mature pancreatic islet-like cell clusters differentiated from embryonic stem cell."Pancreas. 27. e34-e41 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sakurai S, Satake A, Nagata N, Gu Y, Hiura A, Kim DH, Hori H, Tabata Y, Sumi S, Inoue K: "The development of new immunoisolatory devices possessing the ability to induce neovascularization."Cell Transplantation. 12. 527-535 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Qi MG; Gu Y, Sakata N, Kim DH, Shirouzu Y, Yanamoto C, Hiura A, Sumi S, Inoue K: "PVA hydrogel sheet macroencapsulation for the bioartificial pancreas."Biomaterials. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang WJ, Gu Y, Hori H, Sakurai T, Hiura A, Sumi S, Inoue K.: "Subcutaneous transplantation of macroencapsulated porcine pancreatic endocrine cells normalized hyperglycemia in diabetic mice"Transplantation. 76. 290-296 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe H, Sumi S, Kitamura Y, Nio Y, Higami H.: "Immunohistochemical analysis of vascular endothelial growth factor and hepatocyte growth factor, and their receptors, in transplanted islets in rats"Surgery Today. 33. 854-860 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kim DH, Ishii M, Fujimiya M, Qi MG, Nakamura N, Yoshikawa T, Sumi S, Inoue K.: "In vivo functioning and transplantable mature pancreatic isletlike cell clusters differentiated from embryonic stem cell"Pancreas. 27. e34-e41 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakurai S, Satake A, Nagata N, Gu Y, Hiura A, Kim DH, Hori H, Tabata Y, Sumi S, Inoue K.: "The development of new immunoisolatory devices possessing the ability to induce neovascularizaton"Cell Transplantation. 12. 527-535 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Qi MG, Gu Y, Sakata N, Kim DH, Shirouzu Y, Yamamoto C, Hiura A, Sumi S, Inoue K.: "PVA hydrogel sheet macroencapsulation for the bioartificial pancreas"Biomaterials. (発表予定).

    • Related Report
      2003 Annual Research Report
  • [Publications] 角 昭一郎, 日裏 彰人, 顧 元駿, 井上 一知: "再生医療の膵島移植への応用"移植. 38. 133-136 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 角 昭一郎, 井上 一知: "Annual Review2003消化器.戸田剛太郎ほか編,膵移植-現状と展望"中外医療社. 68-73(6) (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wang WJ, et al.: "Restoration of normoglycemia in diabetic mice by xenotransplantation of macroencapsulated porcine pancreatic endocrine cells into a prevascularized subcutaneous site"Transplantation. (発表予定).

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanabe H, et al.: "Immunohistochemical study of Vascular Endothelial Growth Factor (VEGF), Hepatocyte Growth Factor (HGF) and their Receptors in transplanted islets in rats"Surgery Today. (発表予定).

    • Related Report
      2002 Annual Research Report
  • [Publications] Balamurugan AN, et al.: "Bioartificial pancreas transplantation at prevascularized intermuscular space : effect of angiogenesis induction on islet survival"Pancreas. 26(3). 279-285 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Balamurugan AN, et al.: "Hepatocyte growth factor (HGF) is a mitogen and an insulinotropic agent for fetal islet cells in vitro"Pancreas. 26(1). 103-104 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagata N, et al.: "Co-culture of extracellular matrix suppresses the cell death of rat pancreatic islets"J Biomater Sci Polym Ed. 13(5). 579-590 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Balamurugan AN, et al.: "Streptozotocin (STZ) is commonly used to induce diabetes in animal models"Pancreas. 26(1). 102-103 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawakami Y. et al.: "Modified subcutaneous tissue with neovasclarization as the site of pancreatic islet translantation"Cell Transplant. 9. 729-732 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kinoshita N. et al.: "Regulation of cell proliferation using tissue engineering in MIN6 cells"Cell Transplant. 10. 473-477 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wang W.J.et al.: "Effect of basic fibroblast growth factor on insulin secretion from micro-encapsulated pancreatic islets ; An in vitro study"Cell Transplant. 10. 465-471 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Gu Y.J.et al.: "Development of a new method to induce angiogenesis at subcutaneous site of strepotozotocin-induced diabetic rats for islet transplantation"Cell Transplant. 10. 453-457 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Cui W.X, et al.: "The tissue-engineering pancreatic islets : Culturing the rat islets in the chitosan sponge"Cell Transplant. 10. 499-501 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Xu B.Y.et al.: "The innuence of anticomplement synthetic sulfonic polymers on function of pancreatic islets : an in vitro study"Cell Transplant. 10. 413-417 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawakami Y. et al.: "Successful subcutaneous pancreatic islet transplantation uslng angiogenic growth factor releasing device"Pancreas. 23. 375-378 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wang W.J.et al.: "Reversal of diabetes in mice by xenotransplantation of bioartificial pancreas in a prevascularized subcutaneous site"Transplantation. 73. 122-129 (2002)

    • Related Report
      2001 Annual Research Report

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

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