| Project/Area Number |
12671751
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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 |
Plastic surgery
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| Research Institution | NAGASAKI UNIVERSITY |
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Principal Investigator |
HIRANO Akiyoshi Nagasaki University, School of Medicine, associate professor, 医学部, 助教授 (90208835)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Tohru Nagasaki University, School of Medicine, professor, 医学部, 教授 (60136661)
AKITA Sadanori Nagasaki University, Medical School Hospital, assistant professor, 医学部・附属病院, 助手 (90315250)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | cytokines / cranial bone defect / mesenchymal stem cell / Insulin-like growth factor-1, IGF-1 / Leukemia Inhibitory Factor, LIF / Immune tolerance / 幹細胞 / 骨再生 / in vitro / in vivo / 骨代謝 / 頭蓋骨欠損 / 細胞内情報伝達 |
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| Research Abstract |
In order to further analyze the mechanisms and involvement of the cytokine signaling in the bone regeneration, first human keloid-derived fibroblast primary cultures were tested for the' possible resistance against induced apoptosis by ceramide. Ceramide normally induces the fibroblast apoptosis in dose-dependent and in the-dependent Banner; however, fibroblasts derived from keloid showed the G2 arrest by FACS cell sorter and confined by reduced cell number by WST-t assay. When IGF-1 added, keloid fibroblasts resist the ceramide-induced apoptosis. This was positively correlated with IGF-1 receptor expression level. PI-3 inhibitor. Wortmaninn pre-treatment, was markedly abolished inhibition of apoptosis via IGF-1 signaling. In this experiment, the IGF-1 involves in the subsequent signaling via its proper receptor and the molecularly regulated.
On the other hand, on behalf of prolonged skin allograft survival, the effective modalities such as cytokine gene therapy were tested. In between BALB/c and B6D2F1 strain mice Leukemia Inhibitory Factor, LIF plasmid CDNA was injected into the skin allograft donor, LIF expressions were observed in 24 hours and 21 days post-transplantation. The gp130, signal-transduction component of LIF, was expressed along with LIF. When B6D2F1 to BALB/c skin allograftIng, helper T type2 cytokine (IL-10) was observed, thus immune tolerance was indicated for skin allografting in LIF gene therapy.
In bone metabolism, LIF was tested in the cranial bone defect model. LIF was efficiently enhanced the bone formation via osteocyte activation. In combined use of the osteogenic cytokioea (bFGF and BMP-2) and human mesenchymal stem cells in the cranial bone defects demonstrated the significant boneregeneration with sponge carriers underneath.
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