Spiny mice are primed but fail to regenerate volumetric skeletal muscle loss injuries

Skeletal Muscle, 2024 · DOI: https://doi.org/10.1186/s13395-024-00358-y · Published: October 20, 2024

Regenerative Medicine Physiology Musculoskeletal Medicine

Simple Explanation

This study investigates the regenerative capabilities of spiny mice (Acomys cahirinus) in response to volumetric muscle loss (VML) injuries, comparing their response to that of standard laboratory mice (Mus C57BL6/J). VML is a severe muscle injury where a significant amount of muscle tissue is lost. The researchers created VML injuries in the tibialis anterior (TA) muscle of both spiny mice and standard laboratory mice, then monitored and compared their muscle regeneration and functional recovery over a period of three months. While spiny mice have shown remarkable regenerative abilities in other types of injuries, this study found that they did not regenerate VML injuries in the TA muscle any better than standard laboratory mice. Both species failed to recover lost muscle mass or muscle function.

Study Duration

3 months

Participants

Male and female C57BL6/J mice and Acomys cahirinus

Evidence Level

Not specified

Key Findings

1
Neither Acomys nor Mus recovered lost muscle mass or myofiber number within three months following VML injury, and Acomys also failed to recover force production better than Mus.
2
Acomys continued to express eMHC within the injured area even three months following injury, whereas Mus ceased expressing eMHC less than one-month post-injury, suggesting that Acomys muscle was primed, but failed, to regenerate.
3
Acomys exhibited similar levels of fibrosis and fatty infiltration in the VML-injured muscle compared to Mus, which was unexpected given Acomys' typically reduced fibrotic response in other injury models.

Research Summary

The study compared the regenerative response of Acomys and Mus to VML injuries in the tibialis anterior (TA) muscle. Contrary to expectations based on Acomys' regenerative capabilities in other tissues, Acomys did not exhibit superior regeneration of VML injuries in the TA muscle compared to Mus. Both species failed to recover muscle mass, myofiber number, and function following VML, and developed similar fibrotic and fatty infiltration. However, Acomys showed persistent eMHC expression, indicating a potential priming for regeneration that ultimately fails.

Practical Implications

Limits to Regeneration

Demonstrates that even species with high regenerative capacity have limitations, particularly in the context of severe muscle injuries like VML.

Importance of Structural Cues

Suggests that structural and mechanical cues lost in VML injuries may be critical for successful muscle regeneration, even in species that can regenerate other tissues without these cues.

Potential Therapeutic Targets

Highlights the need for further research into the factors that prevent successful muscle regeneration in VML injuries, even when the muscle appears to be primed for regeneration.

Study Limitations

1
The injuries performed in this study were unilateral, and while the animals generally begin ambulating immediately following cessation of anesthesia, they may have favored the injured limb, subjecting it to insufficient force or exercise.
2
Exercise such as voluntary wheel or treadmill running has been reported as beneficial for functional recovery following VML in other rodent models, and thus exercise might provide a further cue to trigger additional regeneration in Acomys which might exceed that in Mus.
3
the PC is an extremely thin layer of muscle, and there may be an injury threshold that the PC does not meet but TA VML injuries exceed.

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