Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 107, Issue 6, Pages 1213-1224Publisher
WILEY
DOI: 10.1002/jbm.a.36617
Keywords
macrophage; intracellular particles; dexamethasone; gene expression; cell-microparticle interactions
Funding
- Department of Veteran's Affairs [I01-RX001097]
- National Heart, Lung, and Blood Institute [R01-HL130037]
- Department of Education GAANN iCARE Fellowship
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Monocyte-derived macrophages play a critical role in directing wound pathology following injury. Depending on their phenotype, macrophages also promote tissue regeneration. However, the therapeutic administration of macrophages with a controlled phenotype is challenging because macrophages are highly plastic and quickly revert to a detrimental, inflammatory phenotype in response to the environment of a damaged tissue. To address this issue, we developed a novel strategy to modulate macrophage phenotype intracellularly through phagocytosis of drug-loaded microparticles. Poly(lactic-co-glycolic acid) microparticles loaded with the anti-inflammatory drug dexamethasone (Dex) were phagocytosed by monocytes and stored intracellularly for at least 5 days. After differentiation into macrophages, cell phenotype was characterized over time with high-throughput gene expression analysis via NanoString. We found that the microparticles modulated macrophage phenotype for up to 7 days after microparticle uptake, with decreases in inflammation-related genes at early timepoints and upregulation of homing- and phagocytosis-related genes at multiple timepoints in a manner similar to cells treated with continuous free Dex. These data suggest that intracellularly loading macrophages with Dex microparticles via phagocytosis could be a unique methodology to selectively modulate macrophage phenotype over time. This strategy would allow therapeutic administration of macrophages for the treatment of a number of inflammatory disease and disorders. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1213-1224, 2019.
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