Antioxidant-loaded sEVs Boost Collagen Turnover in Atrophic Muscles
What if there was a way to stimulate recovery and restore muscle health? A recent study offers hope through the use of antioxidant-loaded small extracellular vesicles (sEVs) derived from healthy muscle cells.
These sEVs have shown the potential to enhance muscle regeneration and, crucially, accelerate collagen turnover—a key factor in tissue repair. By employing 5-FAM-Conjugated Collagen Hybridizing Peptides (F-CHP), researchers gained new insights into how collagen remodeling occurs during muscle recovery, presenting a promising cell-free therapeutic strategy.
Discover how antioxidant-loaded sEVs and CHPs are driving breakthroughs in tissue repair and muscle recovery.
Learn How sEVs Drive Muscle Recovery
When skeletal muscles go unused, they weaken and atrophy, leading to impaired function and reduced quality of life. Since oxidative stress is a key driver of muscle damage during disuse, addressing this is crucial for promoting recovery. During disuse, pericytes—antioxidant-producing cells— become less effective, leading to increased reactive oxygen species (ROS) causing further muscle damage. To test the therapeutic potential of antioxidant-loaded sEVs, researchers isolated pericytes from healthy skeletal muscle and stimulated antioxidant release by exposing the cells to hydrogen peroxide. The resulting sEVs were then injected into atrophic muscle tissues and treated muscles were monitored for signs of recovery.
To assess muscle fiber growth and extracellular matrix (ECM) remodeling, which are critical for understanding how antioxidant-loaded sEVs recover muscle structure, researchers measured the mean cross-sectional area (CSA) of muscle myofibers of sEV-treated mice with and without antioxidant priming. Following sEV treatment, researchers observed an increase in CSA, demonstrating the ability of antioxidant-primed sEVs to promote muscle fiber growth (fig. 4E).
Collagen remodeling, a continuous process in healthy tissue, slows dramatically in atrophic tissue, impairing proper repair and function. To quantify ECM turnover, the researchers used fluorescein-tagged Collagen Hybridizing Peptides (F-CHP), a unique and powerful tool for visualizing and quantifying collagen remodeling. CHPs selectively bind to denatured collagen strands exposed during matrix remodeling, making them ideal for tracking ECM turnover. Results showed increased collagen turnover following sEV treatment compared to sEV controls, providing further evidence that antioxidant-loaded sEVs can stimulate muscle fiber recovery and repair the ECM (fig. 4H, below).
Interestingly, control pericytes (those derived from pericytes not stimulated with hydrogen peroxide) induced collagen remodeling in older mice (24 m.o.) but not in younger mice (2 m.o.), suggesting the response may be age-dependent or influenced by baseline ECM dynamics.
This study highlights a promising cell-free approach for treating skeletal muscle atrophy by leveraging antioxidant-loaded sEVs to promote both muscle fiber regeneration and ECM remodeling. For researchers working in muscle biology, regenerative medicine, or tissue engineering, these findings offer two key takeaways: First, sEVs may serve as an effective tool to combat muscle degeneration and accelerate recovery in atrophic tissues. Second, CHPs provide a reliable method for tracking collagen turnover, making them invaluable for studying ECM dynamics in a range of musculoskeletal disorders. By incorporating CHPs into their research, scientists can gain deeper insights into collagen remodeling processes and explore new therapeutic avenues for enhancing tissue repair in various degenerative conditions.
Wu, YF, et al. “Development of a Cell-Free Strategy to Recover Aged Skeletal Muscle After Disuse.” J Physiol, vol. 601, no. 22, 2023, pp. 5011–5031.