Engineered Extracellular Vesicles Derived from Dermal Fibroblasts Attenuate Inflammation in a Murine Model of Acute Lung Injury
Source abstract
Abstract
Abstract Acute respiratory distress syndrome (ARDS) represents a significant burden to the healthcare system, with ≈200 000 cases diagnosed annually in the USA. ARDS patients suffer from severe refractory hypoxemia, alveolar‐capillary barrier dysfunction, impaired surfactant function, and abnormal upregulation of inflammatory pathways that lead to intensive care unit admission, prolonged hospitalization, and increased disability‐adjusted life years. Currently, there is no cure or FDA‐approved therapy for ARDS. This work describes the implementation of engineered extracellular vesicle (eEV)‐based nanocarriers for targeted nonviral delivery of anti‐inflammatory payloads to the inflamed/injured lung. The results show the ability of surfactant protein A (SPA)‐functionalized IL‐4‐ and IL‐10‐loaded eEVs to promote intrapulmonary retention and reduce inflammation, both in vitro and in vivo. Significant attenuation is observed in tissue damage, proinflammatory cytokine secretion, macrophage activation, influx of protein‐rich fluid, and neutrophil infiltration into the alveolar space as early as 6 h post‐eEVs treatment. Additionally, metabolomics analyses show that eEV treatment causes significant changes in the metabolic profile of inflamed lungs, driving the secretion of key anti‐inflammatory metabolites. Altogether, these results establish the potential of eEVs derived from dermal fibroblasts to reduce inflammation, tissue damage, and the prevalence/progression of injury during ARDS via nonviral delivery of anti‐inflammatory genes/transcripts.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Extracellular vesicles in disease · Thermal Regulation in Medicine · Air Quality and Health Impacts
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Biomedical Engineering The Ohio State University Columbus OH 43210 USA
Biophysics Program The Ohio State University Columbus OH 43210 USA
Biochemistry Program The Ohio State University Columbus OH 43210 USA
Kidney and Urinary Tract Research Center The Abigail Wexner Research Institute Nationwide Children's Hospital Columbus OH 43215 USA
Biomedical Science Graduate Program The Ohio State University Columbus OH 43210 USA
Division of Cardiac Surgery Department of Surgery The Ohio State University Columbus OH 43210 USA
Center for Electron Microscopy and Analysis (CEMAS) The Ohio State University Columbus OH 43212 USA
Department of Materials Science and Engineering The Ohio State University Columbus OH 43210 USA
Division of Pulmonary, Critical Care, and Sleep Medicine The Ohio State University Columbus OH 43221 USA
Department of Pediatrics The Ohio State University Columbus OH 43210 USA
Division of Pediatric Nephrology and Hypertension Nationwide Children's Hospital Columbus OH 43205 USA
Division of General Surgery Department of Surgery The Ohio State University Columbus OH 43210 USA
Dorothy M. Davis Heart & Lung Research Institute The Ohio State University Columbus OH 43210 USA
Gene Therapy Institute The Ohio State University Columbus OH 43210 USA
Funding
National Institutes of Health
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