Abstract
Biomaterial-enabled Macrophage Cell Therapy via Dexamethasone-loaded Microparticles for Pulmonary Fibrosis
Cytotherapy (Oxford, England), v 27(5), S207
May 2025
Abstract
Macrophages are key regulators of tissue repair and regeneration, making them attractive targets in regenerative medicine. As highly phagocytic cells capable of degrading a wide variety of extracellular matrix components, macrophage cell therapy has emerged as a promising prospect for reversing established fibrosis, provided that their phenotype can be precisely controlled. We have developed a strategy to use intracellularly acting, drug-releasing, biodegradable polymeric microparticles (MPs) to engineer macrophages in situ, enabling us to maintain control over their phenotype. In this study, we aimed to investigate the therapeutic effects of macrophages loaded with MPs encapsulating the anti-inflammatory drug Dexamethasone (Dex), which we previously showed induces a fibrosis-resolving phenotype in macrophages, for reversing pulmonary fibrosis.
Mice with established, progressive pulmonary fibrosis (Fig.1a) were treated with GFP+ Dex-MP-loaded macrophages intratracheally. After 7 and 14 days, the phenotypes of transplanted (GFP+) and host (GFP-) macrophages were analyzed via flow cytometry and fibrosis was measured by hydroxyproline assay and micro-CT. As controls, mice were treated with PBS, untreated or blank MP-treated macrophages, or free Dex MPs.
Host macrophages of mice with fibrotic lungs showed increased expression of CD163, CD206, CD301, MERTK, and CD86, which are markers previously identified as drivers of fibrosis. Both transplanted Dex-MP-loaded macrophages and host macrophages in this group (Fig. 1c) expressed lower levels of these markers compared to controls for at least 14 days. Treatment with Dex-MP-loaded macrophages significantly reduced total collagen content compared to untreated animals and to baseline, indicating active clearance of fibrotic tissue (Fig. 1d), a finding that was further corroborated by microCT imaging (Fig. 1e). Mechanistic in vitro and in vivo studies showed that microparticles were transferred to bystander unloaded macrophages (Fig. 1f), indicating a potentially exploitable mechanism of how MP-loaded macrophages can enable targeted drug delivery to modulate the host environment.
Biomaterial-enabled intracellular control of macrophages for cell therapy represents a promising strategy for reversing establishing pulmonary fibrosis.
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Details
- Title
- Biomaterial-enabled Macrophage Cell Therapy via Dexamethasone-loaded Microparticles for Pulmonary Fibrosis
- Creators
- T. Tylek - Drexel UniversityK. Spiller - Drexel University
- Publication Details
- Cytotherapy (Oxford, England), v 27(5), S207
- Publisher
- Elsevier
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Chemical and Biological Engineering
- Other Identifier
- 991022052819204721