Injectable, Pore-Forming Hydrogels for In Vivo Enrichment of Immature Dendritic Cells.
Injectable, Pore-Forming Hydrogels for In Vivo Enrichment of Immature Dendritic Cells.
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DOI：
10.1002/adhm.201500618
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发表时间：
2015-12-09
影响因子：
10
通讯作者：
Mooney DJ
中科院分区：
文献类型：
--
作者：
Verbeke CS;Mooney DJ
基于生物材料的疫苗已经成为直接在体内引起有效免疫应答的有力方法，而不需要离体细胞操作，并且在非炎症背景下调节树突状细胞（DC）应答可以使得能够开发致耐受性疫苗来治疗自身免疫。本研究描述了一种非炎症的可注射水凝胶系统的开发，该系统在体内局部富集DC而不诱导其成熟或活化，作为实现这一目标的第一步。藻酸盐水凝胶，形成孔在原位进行了表征，并用作细胞浸润的物理支架。这些凝胶还适于控制GM-CSF的释放，GM-CSF是DC募集和增殖的有效诱导剂。在体内，GM-CSF从成孔凝胶中的持续释放导致数百万细胞在材料中积累。这些细胞高度富集在CD 11b + CD 11 c + DCs中，并且进一步分析细胞表面标志物表达表明这些DCs是未成熟的。这项研究表明，聚合物递送系统可以介导高数量和百分比的未成熟DC的积累，并可能为进一步开发基于材料的治疗性疫苗提供基础。
Biomaterials-based vaccines have emerged as a powerful method to evoke potent immune responses directly in vivo, without the need for ex vivo cell manipulation, and modulating dendritic cell (DC) responses in a non-inflammatory context could enable the development of tolerogenic vaccines to treat autoimmunity. This study describes the development of a non-inflammatory, injectable hydrogel system to locally enrich DCs in vivo without inducing their maturation or activation, as a first step towards this goal. Alginate hydrogels that form pores in situ were characterized and used as a physical scaffold for cell infiltration. These gels were also adapted to control the release of GM-CSF, a potent inducer of DC recruitment and proliferation. In vivo, sustained release of GM-CSF from the pore-forming gels led to the accumulation of millions of cells in the material. These cells were highly enriched in CD11b+ CD11c+ DCs, and further analysis of cell surface marker expression indicated these DCs were immature. This study demonstrates that a polymeric delivery system can mediate the accumulation of a high number and percentage of immature DCs, and may provide the basis for further development of materials-based, therapeutic vaccines.