| Project/Area Number |
13854020
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Institute for Frontier Medical Sciences, Kyoto University |
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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)
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| 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)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| 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)
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| Keywords | embryonic 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 |
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| 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.
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