Effects of injury size on local and systemic immune cell dynamics in volumetric muscle loss
Year: 2025
Type: article
Abstract: We took a systems approach to the analysis of macrophage phenotype in regenerative and fibrotic volumetric muscle loss outcomes in mice together with analysis of systemic inflammation and of other leukocytes in the muscle, spleen, and bone marrow. Macrophage dysfunction in the fibrotic group occurred as early as day 1, persisted to at least day 28, and was associated with increased numbers of leukocytes in the muscle and bone marrow, increased pro-inflammatory marker expression in splenic macrophages, and changes in the levels of pro-inflammatory cytokines in the blood. The most prominent differences were in muscle neutrophils, which were much more abundant in fibrotic outcomes compared to regenerative outcomes at day 1 after injury. However, neutrophil depletion had little to no effect on macrophage phenotype or on muscle repair outcomes. Together, these results suggest that the entire system of immune cell interactions must be considered to improve muscle repair outcomes.
Source: npj Regenerative Medicine
Institution: Drexel University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: U.S. Department of Health and Human Services, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, University of Pennsylvania, Thomas Jefferson University, National Institutes of Health, Perelman School of Medicine, University of Pennsylvania, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1214792496, G1403651065, G1618664012, G1715775765, G1852790566, Particle-Assisted Control over Macrophage-Neutrophil interactions (Pac-Man), G2766465774, Understanding and Controlling Macrophage Behavior in Angiogenesis, G3344108550, G3428346584, G3822285305, G391053145, G4241894027, G4432337368, G4739483508, G5016707533, G5303466679, G5942036358, G60685716, G6484978735, G672886119, G7066338595, G714764591, G7273793426, G9000000688, G9000127251, G9000138654, G9000170100, G9000199523, G9000266210, Designing Biomaterials to Promote the M1-to-M2 Macrophage Transition and Enhance Angiogenesis
OpenAlex ID: W4407398457