Strategies to reduce dendritic cell activation through functional biomaterial design.
Strategies to reduce dendritic cell activation through functional biomaterial design.
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DOI：
10.1016/j.biomaterials.2012.02.009
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发表时间：
2012-05
期刊：
影响因子：
14
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
Hume, Patrick S.;He, Jing;Haskins, Kathryn;Anseth, Kristi S.
树突状细胞在决定适应性免疫中起着关键作用，并且人们对表征和操纵树突状细胞与生物材料表面之间的相互作用越来越感兴趣。与几种常见的生物材料接触可以诱导未成熟树突状细胞的成熟，但是减少树突状细胞成熟的基质在基于细胞的治疗领域中是特别感兴趣的，其中目标是减少对载有细胞的材料载体的免疫应答。在这项研究中，我们使用基于材料的策略，功能化聚（乙二醇）水凝胶与固定的免疫抑制因子（TGF-β1和IL-10），以减少未成熟的树突状细胞的成熟。TGF-β1和IL-10通常用作体外编程树突状细胞的可溶性因子，并且我们证明当固定在水凝胶表面上时，这些蛋白质保留对树突状细胞的生物活性。在用脂多糖（LPS）和/或细胞因子刺激后，与免疫抑制性水凝胶表面相互作用的树突状细胞系表达减少的成熟标志物，包括IL-12和MHCII。这些免疫调节水凝胶的生物活性进一步用从非肥胖糖尿病（NOD）小鼠分离的原代骨髓树突状细胞（BMDC）证实，如通过活化标志物的减少和活化T细胞的能力的显著降低所定量的。此外，通过引入第二信号以促进BMDC-材料相互作用并结合耐受性信号的呈递，发现多功能PEG水凝胶进一步增加了朝向BMDC的信号传导，如成熟标志物的更大减少所证明的。
Dendritic cells play a key role in determining adaptive immunity, and there is growing interest in characterizing and manipulating the interactions between dendritic cells and biomaterial surfaces. Contact with several common biomaterials can induce the maturation of immature dendritic cells, but substrates that reduce dendritic cell maturation are of particular interest within the field of cell-based therapeutics where the goal is to reduce the immune response to cell-laden material carriers. In this study, we use a materials-based strategy to functionalize poly(ethylene glycol) hydrogels with immobilized immunosuppressive factors (TGF-β1 and IL-10) to reduce the maturation of immature dendritic cells. TGF-β1 and IL-10 are commonly employed as soluble factors to program dendritic cells in vitro, and we demonstrate that these proteins retain bioactivity towards dendritic cells when immobilized on hydrogel surfaces. Following stimulation with lipopolysaccharide (LPS) and/or cytokines, a dendritic cell line interacting with the surfaces of immunosuppressive hydrogels expressed reduced markers of maturation, including IL-12 and MHCII. The bioactivity of these immunomodulatory hydrogels was further confirmed with primary bone marrow dendritic cells (BMDCs) isolated from non-obese diabetic (NOD) mice, as quantified by a decrease in activation markers and a significantly reduced capacity to activate T cells. Furthermore, by introducing a second signal to promote BMDC-material interactions combined with the presentation of tolerizing signals, the mulitfunctional PEG hydrogels were found to further increase signaling towards BMDCs, as evidenced by greater reductions in maturation markers.
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DOI：
10.1016/j.jconrel.2010.05.032
发表时间：
2010-09-15
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Norton LW;Park J;Babensee JE
通讯作者：
Babensee JE
影响因子：
3.1
作者：
Otsu, S;Gotoh, K;Nishizono, A
通讯作者：
Nishizono, A
影响因子：
9.7
作者：
Acharya, Abhinav P.;Dolgova, Natalia V.;Keselowsky, Benjamin G.
通讯作者：
Keselowsky, Benjamin G.
影响因子：
4.4
作者：
LANGMUIR, PB;BRIDGETT, MM;CRISPE, IN
通讯作者：
CRISPE, IN
影响因子：
14
作者：
Acharya, Abhinav P.;Dolgova, Natalia V.;Keselowsky, Benjamin G.
通讯作者：
Keselowsky, Benjamin G.