| Project/Area Number |
15209028
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kyoto University |
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Principal Investigator |
ITOH Hiroshi Kyoto University, Department of Medicine and Clinical Science, Associate Professor, 医学研究科, 助教授 (40252457)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Jun Kyoto University, Institute for Frontier Medical Sciences, Associate Professor, 再生医科学研究所, 助教授 (50335288)
NAKAYAMA Yasuhide National Cardiovascular Center, Department of Biomedical Engineering, Laboratory Chief, 室長 (50250262)
NITO Shinji Tanabe Seiyaku Co., Ltd., Discovery Research Laboratory, Department Manager, 創薬研究所, 主任研究員
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥45,500,000 (Direct Cost: ¥35,000,000、Indirect Cost: ¥10,500,000)
Fiscal Year 2004: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2003: ¥33,930,000 (Direct Cost: ¥26,100,000、Indirect Cost: ¥7,830,000)
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| Keywords | human ES cells / regeneration medicine / progenitor cells / endothelial cells / vascular smooth muscle cells / VEGF / natriuretic peptides / adrenomedullin / ES細胞 / 再生医療 / 血管再生 / 血管新生 |
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| Research Abstract |
From human ES cells we identified and isolated "vascular progenitor cells;VPC", which can be differentiated into both endothelial cells(EC) and vascular smooth muscle cells(VSMC) and organize blood vessel structure in vitro. Human ES cell-derived VPC(hESC-VPC) are TRA-1-Flk1+VEcadherin-PDGFR+ cells. We also discovered that vasodilating peptides, natriuretic peptides and adrenomedullin(AM) can activate cGMP and cAMP cascade, respectively and promote vascular regeneration, by several gene-engineered mice for these peptides, which we developed and by adenovirus-mediated gene transfer technique. Furthermore, we demonstrated that AM potently induces endothelial differentiation of mouse ES cell-derived VPC. Transplantation of EC and VSMC at early differentiation stage induced construction of human blood vessels in vivo and enhanced local blood flow to exert therapeutic effectiveness in hindlimb ischemia model or skin ulcer model. By in vitro human vascular development system, using human VPC, we elucidated the gene expression profiling of human undifferentiated ES,VPC and EC or SMC at early differentiation stage. Furthermore, we developed new biomaterial for blood vessel walls and seeded ES cell-derived VPC onto it. VPC in the artificial blood vessel walls were demonstrated to be differentiated into EC and VSMC by pulsatile flow loading.
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