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        Effect of TNF-α and IL-6 on Compact Bone-Derived Cells

        Zhang Yiming,Li Xianqi,Chihara Takahiro,Dong Hongwei,Kagami Hideaki 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.3

        Background: Although bone tissue engineering has already been applied clinically, its regeneration efficacy is not always sufficient. Local inflammatory cytokines are considered as the major factors that induce apoptosis of transplanted cells, thus leading to insufficient new bone formation. In this study, we focused on the effects of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) on differentiation and apoptosis of compact bone-derived cells (CBDCs). Methods: CBDCs were obtained from mouse legs and cultured. The effects of TNF-α and/or IL-6 on the osteogenic differentiation and apoptosis of CBDCs were analyzed in vitro. To confirm the expression of local inflammatory cytokines in vivo, CBDCs were transplanted to the back of immunocompetent mice. Results: IL-6 exerted inconsistent effects on the expression of the different osteogenic markers tested, while significantly upregulating Fas. By contrast, the addition of TNF-α dramatically reduced the expression of all tested osteogenic markers and increased Fas expression. The highest dose of IL-6 could partially reverse the repressive effect of TNF-α, while the addition of IL-6 further increased Fas expression in CBDCs compared to TNF-α alone. The results from in vivo experiments showed the presence of transplants with and without new bone formation. The transplants without bone formation were characterized by higher IL-6 and lower IL-10 expression than those with bone formation, while the expression of TNF-α did not show notable difference. Conclusion: The results of this study suggest an important role for IL-6 in modulating the efficacy of bone tissue engineering, which can affect osteogenic cells both positively and negatively. Background: Although bone tissue engineering has already been applied clinically, its regeneration efficacy is not always sufficient. Local inflammatory cytokines are considered as the major factors that induce apoptosis of transplanted cells, thus leading to insufficient new bone formation. In this study, we focused on the effects of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) on differentiation and apoptosis of compact bone-derived cells (CBDCs). Methods: CBDCs were obtained from mouse legs and cultured. The effects of TNF-α and/or IL-6 on the osteogenic differentiation and apoptosis of CBDCs were analyzed in vitro. To confirm the expression of local inflammatory cytokines in vivo, CBDCs were transplanted to the back of immunocompetent mice. Results: IL-6 exerted inconsistent effects on the expression of the different osteogenic markers tested, while significantly upregulating Fas. By contrast, the addition of TNF-α dramatically reduced the expression of all tested osteogenic markers and increased Fas expression. The highest dose of IL-6 could partially reverse the repressive effect of TNF-α, while the addition of IL-6 further increased Fas expression in CBDCs compared to TNF-α alone. The results from in vivo experiments showed the presence of transplants with and without new bone formation. The transplants without bone formation were characterized by higher IL-6 and lower IL-10 expression than those with bone formation, while the expression of TNF-α did not show notable difference. Conclusion: The results of this study suggest an important role for IL-6 in modulating the efficacy of bone tissue engineering, which can affect osteogenic cells both positively and negatively.

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        Tissue Engineering with Compact Bone-Derived Cell Spheroids Enables Bone Formation around Transplanted Tooth

        Matsumura Nahomi,Li Xianqi,Uchikawa-Kitaya Eri,Li Ni,Dong Hongwei,Chen Kai,Yoshizawa Michiko,Kagami Hideaki 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.2

        BACKGROUND: Although tooth transplantation is a desirable treatment option for congenital defects of permanent teeth in children, transplantation to a narrow alveolar ridge is not feasible. In this study, we investigated the possibility of bone tissue engineering simultaneously with tooth transplantation to enhance the width of the alveolar bone. METHODS: Bone marrow mononuclear cells or cortical bone-derived mesenchymal stromal cell spheroids were seeded onto atelocollagen sponge and transplanted with freshly extracted molars from mice of the same strain. New bone formation around the tooth root was evaluated using micro-computed tomography and histological analysis. Tooth alone, or tooth with scaffold but without cells, was also transplanted and served as controls. RESULTS: Micro-computed tomography showed new bone formation in the furcation area in all four groups. Remarkable bone formation outside the root was also observed in the cortical bone-derived mesenchymal stromal cell group, but was scarce in the other three groups. Histological analysis revealed that the space between the new bone and the root was filled with collagen fibers in all four groups, indicating that the periodontal ligament was maintained. CONCLUSION: This study demonstrates the potential of simultaneous alveolar bone expansion employing bone tissue engineering approach using cortical bone-derived mesenchymal stromal cell spheroids for tooth transplantation. The use of an orthotopic transplantation model may further clarify the feasibility and functional recovery of the transplanted tooth over a longer period.

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