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Studies on regenerative medicine for severe diabetes mellitus by stem cell biology

Research Project

Project/Area Number 16390360
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

SUMI Shoichiro  Kyoto University, Institute for Frontier Medical Sciences, Associate Professor, 再生医科学研究所, 助教授 (80252906)

Co-Investigator(Kenkyū-buntansha) TABATA Yasuhiko  Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (50211371)
SUNAMURA Makoto  Tohoku University, Hospital, Lecturer, 講師 (10201584)
YAMAMOTO Yuichiro  Kyoto University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (60283610)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2005: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2004: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordsstem cell / therapy for diabetes mellitus / bio-artificial pancreas / beta-cell / pancreatic regeneration / pancreatectoy / regenerative medicine / 分化誘導 / バイオ人工膵臓 / 血管新生
Research Abstract

A new method of making bio-artificial pancreas (BAP), macro-encapsulation of islets in PET (polyethyren tetraphutarate) mesh-reinforced PVA (polyvinyl alcohol) gel by freezing and thawing, was developed. This BAP was found to keep islets viable and functional in comparison to normal free islets in vitro. Transplantation of this BAP ameliorated hyperglycemia and improved renal dysfunction and survival in mouse model of insulin-dependent diabetes mellitus. In studying subcutaneous transplantation of BAP, collagen-coated PVA bag, when applied with sustained release micro-sphere of basic FGF (fibroblast growth factor), was found to induce more angiogenesis and improved viability of included islets in comparison to non-coated PVA bag. Islet preservation studies revealed that apoptosis, a major mechanism of islet cell loss in islet transplantation tended to develop early after islet isolation and rapidly progressed during normal culture conditions. On the other hand, cold preservation in University Wisconsin solution was found to inhibit apoptosis. Pancreas regeneration studies in rats suggested that certain factors perhaps including hyperglycemia was activated by major pancreatectomy and maintained regenerative state of the remnant pancreas, since the weight of the remnant-equivalent pancreas was increased only temporally and returned to its normal weight if pancreatic duct corresponding to removed lobes in major pancreatectomy was ligated and left in the place.
In stem cell studies, neuron-like cells obtained in the differentiation studies of mouse embryonic stem cells were found to improve the symptoms of Parkinson's disease in model rats. Differentiation form bone marrow-derived cells and epithelial cells of pancreatic duct to islet cells and electrical cell fusion of bone marrow cells and islet cells were also studied and interesting knowledge toward future studies was accumulated.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (44 results)

All 2006 2005 2004 Other

All Journal Article (38 results) Book (6 results)

  • [Journal Article] Cold preservation of islets in UW solution -with special reference to apoptosis.2006

    • Author(s)
      Shirouzu Y
    • Journal Title

      J Surg Res (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 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
    • Journal Title

      Pancreas 32・3

      Pages: 249-257

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 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., et al.
    • Journal Title

      Pancreas 32

      Pages: 249-257

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cold preservation of islets in UW solution -with special reference to apoptosis.2006

    • Author(s)
      Shirouzu Y
    • Journal Title

      Journal of Surgical Resserach (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of rat-to-mouse bio-artificial pancreas xenotransplantation on diabetic renal damage and survival.2006

    • Author(s)
      Sakata N
    • Journal Title

      Pancreas (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Transplantation of mouse embryonic stem cell-derived neurons into the striatum, subthalamic nucleus and substantia nigra, and behavioral recovery in hemiparkinsonian rats.2005

    • Author(s)
      Inden M
    • Journal Title

      Neuroscience letters 287

      Pages: 151-156

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] 膵島移植と人工臓器2005

    • Author(s)
      角 昭一郎
    • Journal Title

      移植 40・2

      Pages: 122-128

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ラット膵管結紮と切除の影響に関する研究(第2報)2005

    • Author(s)
      角 昭一郎
    • Journal Title

      胆膵の生理機能 21・1

      Pages: 53-58

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Transplantation of mouse embryonic stem cell-derived neurons into the striatum, subthalamic nucleus and substantia nigra, and behavioral recovery in hemiparkinsonian rats.2005

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

      Neuroscience Letters 287

      Pages: 151-156

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pancreas, islet transplantation and artificial organs.(in Japanese)2005

    • Author(s)
      Sumi S., et al.
    • Journal Title

      Japanese Journal of Transplantation 40(2)

      Pages: 122-128

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Subsequent experimental studies in the influence of partial resection and duct ligature of the pancreas on regeneration of rat pancreas.(in Japanese)2005

    • Author(s)
      Sumi S., et al.
    • Journal Title

      The Japanese Journal of Bilio-pancreatic physiology 21(1)

      Pages: 53-58

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 膵・膵島移植と人工臓器2005

    • Author(s)
      角 昭一郎
    • Journal Title

      移植 40・2

      Pages: 122-128

    • NAID

      10016463218

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 膵島十二指腸切除前後の膵内外分泌機能.2004

    • Author(s)
      角 昭一郎
    • Journal Title

      胆膵の生理機能 20・1

      Pages: 27-31

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 膵島(β細胞)の再生医学とその臨床応用の可能性 -膵再生医学の最前線-.2004

    • Author(s)
      角 昭一郎
    • Journal Title

      胆と膵 25・5

      Pages: 267-272

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ES細胞・骨髄細胞と膵再生医療.2004

    • Author(s)
      角 昭一郎
    • Journal Title

      再生医療 3・4

      Pages: 77-84

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] カプセル化膵島と再生医療-実用化への新しい展開とその将来.2004

    • Author(s)
      日裏 彰人
    • Journal Title

      再生医療 3・4

      Pages: 95-100

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] PVA Hydrogel Sheet Macroencapsulation for the Bioartificial Pancreas.2004

    • Author(s)
      Qi M
    • Journal Title

      Biomaterials 25

      Pages: 5885-5892

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Stem Cells and Regenerative Medicine for Diabetes Mellitus.2004

    • Author(s)
      Sumi S
    • Journal Title

      Pancreas 29・3

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pharmacological characteristics of rotational behavior in hemiparkinsonian rats transplanter with mouse embryonic stem cell-derived neurons.2004

    • Author(s)
      Inden M
    • Journal Title

      J Pharmacol Sci 96

      Pages: 53-64

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The efficient prevascularization induced by fibroblast growth factor 2 with a collagen-coated device improves the cell survival of a bioartificial pancreas.2004

    • Author(s)
      Sakurai T
    • Journal Title

      Pancreas 28

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Extremely low frequency magnetic field affects insulin secretion from insulinoma cell line, RIN-m.2004

    • Author(s)
      Sakurai T
    • Journal Title

      Bioelectromagnetics 25

      Pages: 160-166

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 幹細胞と再生医工学.2004

    • Author(s)
      Ray Jui-Fang Tsai
    • Journal Title

      再生医療 3・2

      Pages: 98-107

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Changes in pancreatic function by pancreatoduodenectomy.(in Japanese)2004

    • Author(s)
      Sumi S, et al.
    • Journal Title

      The Japanese Journal of Bilio-pancreatic physiology 20(1)

      Pages: 27-31

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Frontiers in regenerative medicine f the pancreas.(in Japanese)2004

    • Author(s)
      Sumi S., et al.
    • Journal Title

      Journal of Biliary Tract and Pancreas (Japan) 25(5)

      Pages: 267-272

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ES and bone marrow cells in regenerative therapy of the pancreas.(in Japanese)2004

    • Author(s)
      Sumi S, et al.
    • Journal Title

      Regenerative Medicine 3(4)

      Pages: 77-84

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Encapsulated islet and regenerative medicine -A new development of clinical application. (in Japanese)2004

    • Author(s)
      Hiura A., et al.
    • Journal Title

      Regenerative Medicine 3(4)

      Pages: 95-100

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] PVA Hydrogel Sheet Macroencapsulation for the Bioartificial Pancreas.2004

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

      Biomaterials 25

      Pages: 5885-5892

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Stem cells and regenerative medicine for diabetes mellitus.2004

    • Author(s)
      Sumi S., et al.
    • Journal Title

      Pancreas 29

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pharmacological characteristics of rotational behavior in hemiparkinsonian rats transplanted with mouse embryonic stem cell-derived neurons.2004

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

      Journal of Pharmacological Sciences 96

      Pages: 53-64

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The efficient prevascularization induced by fibroblast growth factor 2 with a collagen-coated device improves the cell survival of a bioartificial pancreas.2004

    • Author(s)
      Sakurai T, et al.
    • Journal Title

      Pancreas 28

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Extremely low frequency magnetic field affects insulin secretion from insulinoma cell line, RIN-m.2004

    • Author(s)
      Sakurai T, et al.
    • Journal Title

      Bioelectromagnetics 25

      Pages: 160-166

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] PVA hydrogel sheet macroencapsulation for the bioartificial pancreas.2004

    • Author(s)
      Meirigeng Qi
    • Journal Title

      Biomaterials 25・27

      Pages: 5885-5892

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Stem cells and regenerative medicine for diabetes mellitus.2004

    • Author(s)
      Shoichiro Sumi
    • Journal Title

      Pancreas 29・3

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The efficient prevascularization induced by fibroblast growth factor 2 with a collagen-coated device improves the cell survival of a bioartificial pancreas.2004

    • Author(s)
      Tomonori Sakurai
    • Journal Title

      Pancreas 28・3

    • Related Report
      2004 Annual Research Report
  • [Journal Article] An extremely low frequency magnetic field attenuates insulin secretion from the insulinoma cell line, RIN-m.2004

    • Author(s)
      Tomonori Sakurai
    • Journal Title

      Bioelectromagnetics 25・3

      Pages: 160-166

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 膵島(β細胞)の再生医学とその臨床応用の可能性-膵再生医学の最前線-2004

    • Author(s)
      角 昭一郎
    • Journal Title

      胆と膵 25・5

      Pages: 267-272

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ES細胞・骨髄細胞と膵再生医療2004

    • Author(s)
      角 昭一郎
    • Journal Title

      再生医療 3・4

      Pages: 77-84

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cold preservation of islets in UW solution -with special reference to apoptosis.

    • Author(s)
      Shorouzu Y, et al.
    • Journal Title

      Journal of Surgical Research (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 医学書院、「今日の治療指針2004」2004

    • Author(s)
      角 昭一郎
    • Total Pages
      1669
    • Publisher
      膵嚢胞,膵癌.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] (株)エヌ・ティー・エス、新改訂・表面科学基礎と応用.2004

    • Author(s)
      角 昭一郎
    • Total Pages
      1531
    • Publisher
      人工膵臓.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 日本評論社、「糖尿病2005」2004

    • Author(s)
      日裏 彰人
    • Total Pages
      292
    • Publisher
      膵島の再生医療.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Artificial pancreas(in Japanese), Basic and Applied Science of the Surface2004

    • Author(s)
      Sumi S., et al.
    • Total Pages
      1531
    • Publisher
      NTS Book Co.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Regenerative medicine of the islet.(in Japanese), Tounyoubyou 20052004

    • Author(s)
      Hiura A., et al.
    • Total Pages
      292
    • Publisher
      Nippon Hyoron Co.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 糖尿病2005(からだの科学増刊)(分担「膵島の再生医療」)2004

    • Author(s)
      日裏彰人
    • Total Pages
      292
    • Publisher
      日本評論社
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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