| Project/Area Number |
18390232
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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 | Nagoya University |
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Principal Investigator |
MUROHARA Toyoaki Nagoya University, Graduate School of Medicine, Professor (90299503)
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| Co-Investigator(Kenkyū-buntansha) |
KOMORI Kimihiro Nagoya University, Graduate School of Medicine, Professor (40225587)
NUMAGUCHI Yasushi Nagoya University, School of Medicine, Associate Professor (90378224)
SHINTANI Satoshi Nagoya University, University Hospital, Assistant Professor (20309777)
近藤 隆久 名古屋大学, 医学部附属病院, 講師 (00303644)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,450,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2007: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2006: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | regenerative medicine / angiogenesis / cell therapy / gene therapy / endothelial cell / stem cell / therapeutic angiogenesis / endothelial progenitor cell / 血管再生療法 |
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| Research Abstract |
Therapeutic angiogenesis using antologous stem/progenitor cells represents a novel strategy for severely ischemic diseases. Recent reports indicated that adipose tissues could supply adipose-derived stem cells (ASCs). Accordingly, we examined whether implantation of ASCs would augment angiogenesis using a mouse model of hind limb ischemia. C57BL/6J mouse inguinal fat pad was obtained and ASCs were isolated using standard medium.
Fluorescence-activated cell sorter (FACS) analysis revealed that ASCs were Sca-1^+CD31-CD34-flk-1-c-kif-Lin. ASCs expressed vascular endothelial growth factor (VEGF) and stromal cell-derived factor I (SDF-1) mRNAs and proteins. Hind limb ischemia was surgically induced and culture-expanded ASCs(1.0xl0^6cells/animal), PBS or differentiated mature adipocytes(MAs) as control cells were injected into the ischemic tissues. At 3 weeks, the ASC group had a greater laser Doppler blood flow index (0.93±0.08 vs. 0.79±0.14 p<0.05) and a higher capillary density (1.51±0.08 vs. 1.13±0.07 p<0.01) compared to the control group. Implantation ofASCs increased circulating EPCs measured by FACS and culture assay. SDF-I mRNA abundance at ischemic tissues and serum SDF-1 levels were greater in the ASC group than control group. Finally, intraperitoneal injection of an anti-SDF-1 neutralizing antibody reduced therapeutic efficacies of ASCs implantation.
Adipose tissue would be a valuable source for cell-based therapeutic angiogenesis. Moreover, SDF-1 may play a pivotal role in the ASCs-mediated angiogenesis at least in part by facilitating mobilization of EPCs.
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