Abstract
BIOMATERIAL-ENABLED MACROPHAGE CELL THERAPY VIA DEXAMETHASONE-LOADED MICROPARTICLES FOR REGENERATIVE MEDICINE
Cytotherapy (Oxford, England), v 26(6), pS200
Jun 2024
Abstract
Macrophages are key players of the innate immune system and the primary initiators of inflammatory responses. They are involved in dfferent stages of wound healing and tissue repair and are necessary for the resolution of diseases, making them an attractive choice for cell therapy applications. However, macrophage cell therapy, in particular for applications in regenerative medicine, has been limited by their tendency to rapidly change phenotype in response to local cues and manufacturing challenges, particularly because macrophages are resistant to genetic modification and change their phenotype in response to it. Thus, in our approach to solving these challenges, we utilize biomaterial-enabled macrophage cell therapy via polymeric microparticles (MPs) loaded with small molecular drugs that allow intracellular control over the macrophage phenotype.
For the intracellular delivery of small molecules, murine macrophages were incubated in vitro with MPs encapsulating Dexamethasone, an anti-inflammatory, anti-fibrotic intracellular acting drug, or blank MPs (1-3 µm) for up to 24 hours. Macrophages exhibited an anti-inflammatory, anti-fibrotic macrophage phenotype (by downregulation of e.g., TNFa, IL1b, CD86; upregulation of CD163, CD206, MMP8) with increased phagocytic capacity. Upon administration directly to fibrotic lungs of mice, macrophages containing Dex-MPs were maintained, compared to blank MPs loaded macrophages, the expression pattern of the pro-reparative markers CD206 and CD301b and downregulation of MH2 and CD86. Additionally, in a model of subcutaneous implantation of Dex MP macrophage-loaded collagen scaffolds, we further observed phenotypical changes in host macrophages compared to the controls. After seven days, host macrophages showed increased CD163, CD206, and CD301 and decreased CD86 expression, indicating that Dex MP macrophages have the potential to modulate the host environment. The next experiments will explore the effects of Dex MP-loaded macrophages on tissue remodeling and host cell control in pulmonary fibrosis.
In conclusion, biomaterial-enabled intracellular control of macrophages for cell therapy is a promising strategy as it shows potential for phenotype maintenance and host cell control. Furthermore, this approach allows the induction of a complex phenotype that can be adjusted for several applications by changing and modifying drug or biomaterial components.
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Details
- Title
- BIOMATERIAL-ENABLED MACROPHAGE CELL THERAPY VIA DEXAMETHASONE-LOADED MICROPARTICLES FOR REGENERATIVE MEDICINE
- Creators
- T. Tylek - Drexel UniversityJ. Wong - University of PennsylvaniaA. Vaughan - University of PennsylvaniaK. Spiller - Drexel University
- Publication Details
- Cytotherapy (Oxford, England), v 26(6), pS200
- Publisher
- Elsevier
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Other Identifier
- 991021879760504721