| Project/Area Number |
15390538
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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 |
Plastic surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
TORII Shuhei Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (60115607)
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| Co-Investigator(Kenkyū-buntansha) |
KAMEI Yuzuru Nagoya University, Graduate School of Medicine, Associated Professor, 大学院・医学系研究科, 助教授 (10257678)
TAKADA Toru Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (40362248)
KITAGAWA Yasuo Nagoya University, Graduate School of Bioagricultural Sciences, Professor, 大学院・生命農学研究科, 教授 (50101168)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥12,200,000 (Direct Cost: ¥12,200,000)
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| Keywords | adipose-derived stem cell / fat tissue / Reconstruction / low-serum medium / laminin / adult stem cell / 間葉系幹細胞 / 生体幹細胞保有因子 / 形成外科 / 脂肪 / 形成外科術 / 無血清化 |
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| Research Abstract |
Appreciation of ubiquity and plasticity of adult stem cells has changed dramatically in the last several years. Self-renewing stem cells have been demonstrated in various adult tissues and they show potential of differentiation along unexpected pathways, giving rise to the cells of not only the same developmental linage but also the linage different from which the stem cells were derived. Well-characterized example is bone marrow-derived stem cells that can differentiate in vitro into osteoblasts, chondrocytes, adipocytes and myoblasts, and can be incorporated in vivo into bone, skeletal muscle, lung and gut and the central nervous system. Another example of adult stem cell is adipose-derived stem cell(ASC) that can differentiate along mesenchymal linage to produce adipocytes, chondrocytes, myocytes and osteoblasts and also along neuronal linage.
In this research, we fond that population of undifferentiated stem cells in stromal vascular fraction(SVF) dispersed from adipose tissue can b
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e expanded only by culturing in a low-serum medium containing fibroblast growth factor(FGF)-2. Under the culture condition decreased with differentiation factors contained in a serum, undifferentiated stem cell population exhibited almost unlimited potential of proliferation and resulting cells showed high frequency of differentiation into adipocytes, osteoblasts and chondrocytes. We thus suggest that the stem cells in adipose tissues maintain their self-renewing cycle in low-serum medium retaining the potential of multiple differentiations. Recent impact among scientist studying ASC is that adipose tissues contain large amount of common progenitor for mesenchymal stem cell and angioblast (meso-angioblast). Fluorescence-activated cell sorter analysis showed such stem cells (CD34+) account for the major population of the cells in stromal vascular fraction dispersed from adipose tissues. Having large number of multi-potent stem cells in adipose tissues, the next question to be addressed is how ASCs remain quiescent without spontaneous proliferation and differentiation.
We have ever shown that gene expression of laminin α4 chain increases depending on adipose conversion of 3T3-L1 fibroblasts. Laminin G-like domain (LG) 4 module of a4 chain has strong affinity for syndecans. Finding that α4 LG3-5 is cleaved from laminin-8 (α4β1γ1) in vivo, we explored its function as a ligand blocking FGF-2 signaling. In mouse de novo adipogenesis at the site of injection of Matrigel plus FGF-2,addition of α4 LG4-5 at 20 nM suppressed the adipogenesis completely. Activity of LG4-5 was cryptic within the whole structure of G domain since α4 LG1-5 showed only weak effect. Suppressive effect of α4 LG4 was lost in its mutants with reduced heparin-binding activity. Antibodies against extracellular (but not cytoplasmic) domain of syndecan-2 and 4 suppressed the adipogenesis. Thus, FGF-signaling via syndecans appeared to be blocked by α4 G domain fragments due to their competitive binding to syndecans. Less
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