| Project/Area Number |
12470161
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | The Cardiovascular Research Institute, Kurume University |
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Principal Investigator |
MUROHARA Toyoaki Cardiovascular Research Institute, Kurume University Assistant Professor, 循環器病研究所, 講師 (90299503)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Ken-ichiro Dept. of Internal Medicine 3, Kurume Univ. School of Med. Associate Professor, 医学部, 助手 (70320190)
SHINTANI Satoshi Dept. of Internal Medicine 3, Kurume Univ. School of Med. Associate Professor, 医学部, 助手 (20309777)
IKEDA Hisato Dept. of Internal Medicine 3, Kurume Univ. School of Med. Associate Professor, 医学部, 助教授 (50168134)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2001: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2000: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | Endothelial progenitor cell / Ischemic heart disease / Vasculogenesis / Arteriosclerosis obliterans / Angiogenesis / Endothelial cell / Vascular regeneration / Collateral vessel |
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| Research Abstract |
Endothelial precursor cells (EPCs) and hematopoietic stem cells (HS Cs) differentiate from common precursor cells, and these cells originate from bone marrow in adults. Because granulocyte-colony stimulating factor (G-CSF) is a potent hematopoietic cytokine and can induce HSC mobilization, we tested whether GCSF could mobilize EPCs into peripheral circulation and modulate ischemia-induced postnatal neovascularization in vivo. Recombinant human G-CSF (rhG-CSF) had functional activity in rats because injection of rhG-CSF (5 microg/kg/d x 7d, n=5) on the dorsal skin increased circulating leukocyte count, which returned to the baseline levels after the cessation of the injection. Peripheral blood mononuclear cell (MNC) culture assay revealed that the number of differentiated EPCs significantly decreased after rhG-CSF treatment (42±7 vs. 13±2 EPCs /field, p<.0.01). We then tested whether rhG-CSF modulates neovascularization in a rat model of hindlimb ischemia. Control rats received saline,
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while rats in the treatment group received rhG-CSF on the dorsal skin starting on the day of limb surgery for ischernia. Laser Doppler blood flowmetry and tissue capillary density analysis revealed that the ischeniia-induced neovascularizalion and blood flow recovery did not differ significantly between the two groups. In rats, rhG-CSF seemed to be a negative regulator for the in vivo EPC mobilization although it did not alter the extent of the ischemia-induced postnatal neovascularization.
We next examined whether hypoxia would modulate differentiation and function of human PB-MN Cderived EPCs. Subset of PB-MNCs gave rise to EPC-like attaching (AT) cells under eitherjiormoxic or hypoxic conditions. However, hypoxia much enhanced the differentiation of AT cells from PB-MN Cs compared to nomioxia. In vivo neovascularization efficacy was significantly enhanced by hypoxiaconditioned AT cells compared to normoxia-conditioned AT cells when cells were transplanted into the ischemic hindlimb of immunodeficient nude rats. in conclusion, hypoxia directly stimulated differentiation of EPC-like AT cells from human PB-MNC culture. Moreover, hypoxia enhanced the angiogenic efficacies of AT cells. Less
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