Differential effects of agarose and poly(lactic-co-glycolic acid) on dendritic cell maturation.

Differential effects of agarose and poly(lactic-co-glycolic acid) on dendritic cell maturation.
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DOI:
10.1002/jbm.a.30798
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发表时间:
2006-11
期刊:
Journal of biomedical materials research. Part A
影响因子:
--
通讯作者:
Mutsumi Yoshida;J. Babensee
Mutsumi Yoshida;J. Babensee
中科院分区:
其他
文献类型:
--
作者:
Mutsumi Yoshida;J. Babensee

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生物材料在组合产品中的应用,其中生物材料与生物成分一起呈现给宿主,这促使需要了解生物材料相关佐剂在针对与此类产品相关的抗原的免疫反应中的佐剂效应。我们以前已经证明了一种在组织工程和疫苗输送中常用的聚合物,聚乳酸-羟基乙酸(PLGA)在体内发挥了佐剂作用,这是由PLGA诱导的树突状细胞(DC)在体外成熟所支持的。在本研究中,比较琼脂糖凝胶和PLGA对DC体外成熟的影响,以建立不同的生物材料效应。用琼脂糖凝胶或PLGA微球或薄膜处理人单核细胞来源的DC,通过共刺激分子和MHC-II类分子的表达、同种异体刺激能力和促炎细胞因子的分泌来检测其成熟效果。DC成熟表型的直接比较表明,PLGA对DC成熟的刺激作用强于琼脂糖凝胶,这种成熟不受微粒吞噬作用的影响。而经琼脂糖凝胶处理的DC在初始刺激后24 h核因子kappaB(NFkappaB)活性升高。综上所述,这些结果显示了不同生物材料对DC成熟的影响,证实了PLGA的成熟效应,并为生物材料佐剂效应在组合产品中的应用提供了筛选方法。
Application of biomaterials in combination products in which the biomaterial is presented to the host with a biological component prompts the need for understanding the biomaterial-associated adjuvant effect in the immune response against antigens associated with such a product. We have previously demonstrated that a polymer commonly used in tissue engineering and vaccine delivery, poly(lactic-co-glycolic acid) (PLGA), exerts an adjuvant effect in vivo, which was supported by PLGA-induced dendritic cell (DC) maturation in vitro. In this study, the effects of agarose and PLGA on DC maturation were compared in vitro to establish differential biomaterial effects. Human monocyte-derived DCs were treated with agarose or PLGA microparticles or films, and their maturation effect was measured as expression of costimulatory and MHC class II molecules, allostimulatory capacity, and proinflammatory cytokine secretion. Direct comparison of DC maturation phenotype indicated that PLGA was a stronger stimulus of DC maturation than agarose, and this maturation was not affected by microparticle phagocytosis. However, agarose-treated DCs showed higher activation of nuclear factor kappaB (NFkappaB) 24 h after the initial stimulation of DCs. Taken together, these results demonstrate differential biomaterial effects on DC maturation, substantiating the maturation effect of PLGA, and provide screening methods for biomaterial adjuvant effect for applications in combination products.