Title: Particle- and drug-screening for macrophage phenotype control
Abstract:
Macrophages, integral to the innate immune system, are involved in numerous disease and injury models due to their unique ability to interact with neighboring cells (Watanabe et al., 2019). Consequently, macrophage cell therapy has become a promising approach for various medical conditions, including inflammatory disorders, autoimmune diseases, tissue regeneration, and cancer immunotherapy (Na et al., 2023). However, these cells can quickly alter their phenotype in response to local cues, often assuming an undesired state. Thus, maintaining their phenotype becomes critical in cell therapy. Our laboratory uses poly(lactic-co-glycolic acid) (PLGA) microparticles to intrinsically control macrophage phenotype, even against external stimuli. In this work, we explored the effects of particle size on drug release kinetics and macrophage phenotype as well as screened potential therapeutic drug candidates for macrophage cell therapy in fibrotic models. We determined the effect of particle size on drug release kinetics and subsequent effects on macrophage phenotype. In addition, we identified Drug G as a promising macrophage modulator for cell therapy in models, like volumetric muscle loss and pulmonary fibrosis. Future work will focus on evaluating particle size and drug on tissue regeneration in vivo. By elucidating these interactions, we aim to develop specific and tailored strategies for enhanced macrophage-based cell therapies in fibrotic conditions.
Abstract:
Macrophages, integral to the innate immune system, are involved in numerous disease and injury models due to their unique ability to interact with neighboring cells (Watanabe et al., 2019). Consequently, macrophage cell therapy has become a promising approach for various medical conditions, including inflammatory disorders, autoimmune diseases, tissue regeneration, and cancer immunotherapy (Na et al., 2023). However, these cells can quickly alter their phenotype in response to local cues, often assuming an undesired state. Thus, maintaining their phenotype becomes critical in cell therapy. Our laboratory uses poly(lactic-co-glycolic acid) (PLGA) microparticles to intrinsically control macrophage phenotype, even against external stimuli. In this work, we explored the effects of particle size on drug release kinetics and macrophage phenotype as well as screened potential therapeutic drug candidates for macrophage cell therapy in fibrotic models. We determined the effect of particle size on drug release kinetics and subsequent effects on macrophage phenotype. In addition, we identified Drug G as a promising macrophage modulator for cell therapy in models, like volumetric muscle loss and pulmonary fibrosis. Future work will focus on evaluating particle size and drug on tissue regeneration in vivo. By elucidating these interactions, we aim to develop specific and tailored strategies for enhanced macrophage-based cell therapies in fibrotic conditions.