Effects of injury size on local and systemic immune cell dynamics in volumetric muscle loss
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. Differences in expression of macrophage phenotype markers occurred as early as day 1, persisted to at least day 28, and were 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.
Authors
- Ricardo Whitaker (ORCID: https://orcid.org/0009-0003-1813-914X)
- E. O'Brien (ORCID: https://orcid.org/0000-0002-6876-0183)
- Thomas Li (ORCID: https://orcid.org/0000-0002-4207-4652)
- Samuel Sung
- Kara L. Spiller (ORCID: https://orcid.org/0000-0001-7798-1490)
- Benjamin I. Binder‐Markey (ORCID: https://orcid.org/0000-0001-8920-4381)
- Ryan J. Petrie (ORCID: https://orcid.org/0000-0001-9780-4969)
- Gregory E. Risser (ORCID: https://orcid.org/0000-0002-5012-9908)
- Tina Tylek (ORCID: https://orcid.org/0000-0003-1102-8431)
- Lin Han (ORCID: https://orcid.org/0000-0003-4180-1288)
- Phoebe Ellin Chua
Institutions
- Drexel University (US)
Publication Details
- Journal
- npj Regenerative Medicine
- Published
- 2025-02-12
- DOI
- https://doi.org/10.1038/s41536-025-00397-z
- Citations
- 3
- Primary Topic
- Exercise and Physiological Responses
- Type
- article
- Field-Weighted Citation Impact
- 3.08
Funders
- 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 Arthritis and Musculoskeletal and Skin Diseases