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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Biomaterial-mediated Reprogramming of Monocytes via Microparticle Phagocytosis for Sustained Modulation of Macrophage Phenotype
Acta biomaterialia, v 101
13 Nov 2019
PMID: 31731024
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Monocyte-derived macrophages orchestrate tissue regeneration by homing to sites of injury, phagocytosing pathological debris, and stimulating other cell types to repair the tissue. Accordingly, monocytes have been investigated as a translational and potent source for cell therapy, but their utility has been hampered by their rapid acquisition of a pro-inflammatory phenotype in response to the inflammatory injury microenvironment. To overcome this problem, we designed a cell therapy strategy where monocytes are exogenously reprogrammed by intracellularly loading the cells with biodegradable microparticles containing an anti-inflammatory drug in order to modulate and maintain an anti-inflammatory phenotype over time. To test this concept, poly(lactic-co-glycolic) acid microparticles were loaded with the anti-inflammatory drug dexamethasone (Dex) and administered to primary human monocytes for four hours to facilitate phagocytic uptake. After removal of non-phagocytosed microparticles, microparticle-loaded monocytes differentiated into macrophages and stored the microparticles intracellularly for several weeks
in vitro
, releasing drug into the extracellular environment over time. Cells loaded with intracellular Dex microparticles showed decreased expression and secretion of inflammatory factors even in the presence of pro-inflammatory stimuli up to 7 days after microparticle uptake compared to untreated cells or cells loaded with blank microparticles, without interfering with phagocytosis of tissue debris. This study represents a new strategy for long-term maintenance of anti-inflammatory macrophage phenotype using a translational monocyte-based cell therapy strategy without the use of genetic modification. Because of the ubiquitous nature of monocyte-derived macrophage involvement in pathology and regeneration, this strategy holds potential as a treatment for a vast number of diseases and disorders.
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Details
- Title
- Biomaterial-mediated Reprogramming of Monocytes via Microparticle Phagocytosis for Sustained Modulation of Macrophage Phenotype
- Creators
- Kathryn L. Wofford - Drexel UniversityBhavani S. Singh - Drexel UniversityD. Kacy Cullen - University of PennsylvaniaKara L. Spiller - Drexel University
- Publication Details
- Acta biomaterialia, v 101
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000504504300017
- Scopus ID
- 2-s2.0-85075936384
- Other Identifier
- 991019168972804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials