Effects of Injury Size on Local and Systemic Immune Cell Dynamics in Volumetric Muscle Loss

Overview

Journal NPJ Regen Med

Date 2025 Feb 12

PMID 39939310

Authors

Ricardo Whitaker

Samuel Sung

Tina Tylek

Gregory E Risser

Erin M OBrien

Phoebe Ellin Chua

Thomas Li

Ryan J Petrie

Lin Han

Benjamin I Binder-Markey

Kara L Spiller

Affiliations

Soon will be listed here.

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. 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.

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