Toward specific macrophage phenotype characterization and novel strategies for macrophage phenotype modulation

Chen, Hongyu
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Chan, Deva
Palermo, Edmund
Gilbert, Ryan
Hahn, Mariah
Issue Date
Biomedical engineering
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This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute (RPI), Troy, NY. Copyright of original work retained by author.
Full Citation
Macrophages are highly plastic immune cells that play a variety of critical roles throughout the duration of the host response. Classically activated macrophages, primed by interferon-gamma or bacteria-derived products, are known to clear pathogens and induce inflammation through secretion of pro-inflammatory mediators. In the past two decades, the 2-dimensional concept of macrophage activation has been expanded to incorporate a multi-dimensional landscape that is only beginning to be understood. Due to the highly plastic nature of macrophages and subtle changes in functions among populations and subpopulations, it is important to understand macrophage activation profile within specific disease contexts. The overarching focus of this thesis is two-fold: 1) the establishment of in vitro systems to understand the role of macrophage phenotype for vocal-fold regeneration and 2) to develop and assess novel approaches to control macrophage activation toward a desired outcome. In the first part of this thesis, we setup a 3-dimensional, in vitro co-culture using vocal fold cell types to assess the impact of select cytokine treatments on vocal-fold myofibroblasts. In the same study, we identify potential associations between specific vocal fold fibroblast phenotypes and macrophage activation states. These results indicate that a transition from a pro-inflammatory (M1) macrophage phenotype to an anti-inflammatory/pro-resolving (M2) macrophage phenotype may be desirable for normal, scarless healing of the vocal fold lamina propria. Using this knowledge, the next goal of this thesis was to examine novel strategies to promote this transition. Specifically, we investigate the capacity of novel sophorolipid esters and hyperosmolar potassium (K+) treatments to influence macrophage activation. In sum, this work not only deepens our understanding of the complex interactions between fibroblasts and macrophages, but also suggests novel therapies that could be implemented to influence these interactions. In the long-term, we envision that this work will have a broader impact, providing potential treatments for other conditions where fibroblast-macrophage dysregulation has a pathological role.
School of Engineering
Dept. of Biomedical Engineering
Rensselaer Polytechnic Institute, Troy, NY
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