title: Injectable, Pore-Forming Hydrogels for In Vivo Enrichment of Immature Dendritic Cells.
abstract: 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 noninflammatory context could enable the development of tolerogenic vaccines to treat autoimmunity. This study describes the development of a noninflammatory, injectable hydrogel system to locally enrich DCs in vivo without inducing their maturation or activation, as a first step toward this goal. Alginate hydrogels that form pores in situ are characterized and used as a physical scaffold for cell infiltration. These gels are also adapted to control the release of granulocyte-macrophage colony stimulating factor (GM-CSF), a potent inducer of DC recruitment and proliferation. In vivo, sustained release of GM-CSF from the pore-forming gels leads to the accumulation of millions of cells in the material. These cells are highly enriched in CD11b(+) CD11c(+) DCs, and further analysis of cell surface marker expression indicates these DCs are 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.
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
authors.forename: Catia S
authors.initials: CS
authors.lastname: Verbeke
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D020100:Hydrogels / Q000008:administration & dosage*; D007267:Injections / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D014612:Vaccines / Q000008:administration & dosage
chemical_list: D015415:Biomarkers; D020100:Hydrogels; D014612:Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: alginate; dendritic cells; gold nanoparticles; hydrogels; immunotherapy