| Project/Area Number |
17209028
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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 Prefectural University of Medicine |
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Principal Investigator |
MATSUBARA Hiroaki Kyoto Prefectural University of Medicine, School of Medicine Department of Medicine, Professor (10239072)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Tomosaburo Kyoto Prefectural University School of Medicine, Department of Medicine, Instructor (20381973)
OH Hidemasa Kyoto University, Department of Medicine, Associate Professor (50372579)
辰巳 哲也 京都府立医科大学, 医学研究科, 講師 (20254328)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥49,530,000 (Direct Cost: ¥38,100,000、Indirect Cost: ¥11,430,000)
Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2006: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2005: ¥20,670,000 (Direct Cost: ¥15,900,000、Indirect Cost: ¥4,770,000)
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| Keywords | cardiac stem cell / heart failure / regeneration / cardiomyogenesis / 血管新生 / 多能性幹細胞 / 心筋前駆細胞 / 血管前駆細胞 |
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| Research Abstract |
Recent studies have shown that cardiac stem cells (CSCs) from the adult heart can give rise to functional cardiomyocytes; however, the definite surface markers to identify a definitive single entity of CSCs and the molecular mechanisms regulating their growth have remained unknown. Here we demonstrate a single-cell deposition analysis to isolate individually selected CSCs from adult hearts and investigate the signals required for their proliferation and survival. Clonally proliferated CSCs express stem cell antigen-1 (Sca-1) with embryonic stem (ES) cell-and mesenchymal cell-like characteristics and are associated with telomerase reverse transcriptase (TERT). Using a transgene that expresses a GFP reporter under the control of the TERT promoter, we demonstrated that TERT^<GFP+> fractions from the heart were entiched for cell expressing Sca-1. Knockdown of Sca-1 transcripts in CSCs led to retarded ex vivo expansion and apoptosis through Akt inactivation. We also show that ongoing CSC proliferation and survival after direct cell-grafting into ischemic myocardium require Sca-1 to upregulate the secreted paracrine effectors that augment neoangiogenesis and limit cardiac apoptosis, Thus, Sca-1 might bean essential component that promotes CSC proliferation and survival to directly facilitate early engraftment, and that indirectly exerts the effects on late cardiovascular differentiation after CSC transplantation.
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