| Project/Area Number |
18591413
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Yamaguchi University |
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Principal Investigator |
FURUTANI Akira Yamaguchi University, University Hospital, Associate Professor (90346552)
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| Co-Investigator(Kenkyū-buntansha) |
HAMANO Kimikazu Yamaguchi University, Graduate School of Medicine, Professor (60263787)
LI Tao-sheng Yamaguchi University, Graduate School of Medicine, Assistant Professor (50379997)
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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 |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Ischemia / Bone marrow stem cells / Cytokines |
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| Research Abstract |
Therapeutic angiogenesis by bone marrow cells (BMCs) implantation is a promising treatment for ischemic diseases. It is well known that many inflammatory cytokines are released in ischemic tissue, especially in the acute phase. We investigated whether the transient increase of cytokines in the acute ischemic tissue influences cell-based therapeutic angiogenesis.
Ischemic limb models were created in C57BL/6 mice and used 24 hours (acute) or 2 weeks (chronic) after ischemia. We extracted total tissue protein from the acute and chronic ischemic limbs muscles and found that inflammatory cytokines (IL-1β, bFGF, and MCP-1) were robustly increased in acute ischemic limbs, but that this increase had almost disappeared in the chronic ischemic limbs. The survival, adhesion, and migration of BMCs were significantly better after culture with 1 mg/ml tissue protein from the acute ischemic limbs than with that from the chronic ischemic and non-ischemic limbs (p < 0.05) ; however, the difference was relatively weak between the chronic ischemic limbs and the non-ischemic limbs. For the in vivo study, we implanted BMCs into the acute and chronic ischemic limbs of mice. The survival of BMCs was significantly better in the acute ischemic limbs than in the chronic ischemic limbs (p < 0.01). Compared with control treatment, improved blood flow was seen in the acute ischemic limbs (p < 0.01), but not in the chronic ischemic limbs (p = 0.27). The endothelial differentiation of surviving BMCs was found in the acute ischemic limbs.
Our findings suggest that the transient increase of cytokines in the acute ischemic tissue is beneficial for cell-based therapeutic angiogenesis.
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