Effect of poly(lactic-co-glycolic acid) contact on maturation of murine bone marrow-derived dendritic cells.
Effect of poly(lactic-co-glycolic acid) contact on maturation of murine bone marrow-derived dendritic cells.
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DOI：
10.1002/jbm.a.30832
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Mutsumi Yoshida;Jessica Mata;J. Babensee
中科院分区：
文献类型：
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作者：
Mutsumi Yoshida;Jessica Mata;J. Babensee
了解生物材料的佐剂效应及其机制对于有效设计和选择适用于特定应用的材料至关重要。我们以前已经表明，聚（乳酸-共-乙醇酸）（PLGA），组织工程中最常研究的聚合物之一，支持佐剂效应，通过增强免疫反应对共同交付的模型抗原，这是依赖于生物材料的形式。此外，我们已经表明，PLGA诱导人外周血单核细胞来源的树突状细胞（DC）在体外成熟。在这项研究中，PLGA接触对小鼠骨髓来源的DC成熟的影响进行了研究，部分解释了观察到的生物材料佐剂效应。用PLGA微粒或膜处理来自C57 BL 6小鼠的骨髓衍生的DC导致这些细胞的成熟，如通过共刺激分子CD 80和CD 86的表达增加以及促炎细胞因子TNF-α和IL-6的产生所例示的。这些结果表明，PLGA接触诱导鼠DC的成熟，支持我们对人DC的观察。随着这项研究中开发的技术和结果，我们未来的目标是利用转基因小鼠模型来描绘生物材料诱导DC成熟的机制。
Understanding of biomaterial adjuvant effect and its mechanisms is essential for the effective design and selection of appropriate materials for specific applications. We have previously shown that poly(lactic-co-glycolic acid) (PLGA), one of the most commonly studied polymers in tissue engineering, supports an adjuvant effect as measured by enhanced immune response against a co-delivered model antigen, which was dependent on the form of the biomaterial. Furthermore, we have shown that PLGA induces the maturation of human peripheral blood mononuclear cell-derived dendritic cells (DCs) in vitro. In this study, the effect of PLGA contact on the maturation of murine bone marrow-derived DCs was investigated in part to explain the biomaterial adjuvant effect observed. Treatment of bone marrow-derived DCs from C57BL6 mice with PLGA microparticles or films lead to maturation of these cells as exemplified by increased expression of co-stimulatory molecules CD80 and CD86 and production of proinflammatory cytokines TNF-alpha and IL-6. These results suggest that PLGA contact induces maturation of murine DCs, supporting our observations with human DCs. With the techniques developed in this study and given the results, our future goal is to utilize transgenic murine models to delineate the mechanisms of biomaterial-induced DC maturation.