Abstract
The spiny mouse, Acomys cahirinus, is an adult mammal capable of remarkable feats of scar-free tissue regeneration after damage to several organs including the skin and the heart. Here we investigate the regenerative properties of the skeletal muscle of A. cahirinus tibialis anterior in comparison to the lab mouse, Mus musculus. The A. cahirinus TA showed a similar distribution of myosin heavy chain fibre types and a reduced proportion of oxidative fibres compared to M. musculus. There were differences in the matrix components of the TA with regard to collagen VI and the biomechanical properties. A. cahirinus TA regenerated faster with a more rapid induction of embryonic myosin and higher levels of dystrophin than in M. musculus fibres. There were lower levels of inflammation (NF-kB), fibrosis (TGFβ-1, collagens) and higher levels of the anti-inflammatory cytokine Cxcl12. There was a difference in macrophage profile between the two species. After multiple rounds of muscle regeneration the M. musculus TA failed to regenerate muscle fibres and instead produced a large numbers of adipocytes whereas the A. cahirinus TA regenerated perfectly. This clearly improved regeneration performance can be explained by differing levels of growth factors such as adiponectin between the two species.
Highlights
Skeletal muscle is one of the few mammalian tissues which can rapidly repair itself repeatedly throughout life[1,2]
We find that A. cahirinus tibialis anterior (TA) can regenerate slightly faster than M. musculus but the major differences in the two species lie in the macrophage profiles which rapidly infiltrate the damaged muscle, the matrix and biomechanical properties of the muscle and the fact that repeated rounds of regeneration results in degenerated muscles with significant adipocyte infiltration in M. musculus, but perfect regeneration in A. cahirinus
The muscle MHC fibre profiles were similar between M. musculus and A. cahirinus TAs we considered whether there were any differences that could be detected in the ECM components of this muscle because of the role that the ECM plays in maintaining the stem cell niche[20,21,22]
Summary
Skeletal muscle is one of the few mammalian tissues which can rapidly repair itself repeatedly throughout life[1,2]. Satellite cells, located between the basal lamina and the sarcolemma of the myofibre, are the muscle stem cells and provide the source of new cells for regenerated muscle fibres. The fate of the FAPs is controlled by IL-4/IL-13 signaling from eosinophils which inhibits their spontaneous differentiation into adipocytes and instead permits them to generate growth factors for myoblast proliferation and differentiation[26]. This cell type is at the heart of the process of fatty degeneration of skeletal muscle which occurs in myopathies such as Duchenne muscular dystrophy[27]
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