Abstract
Skeletal muscle has a remarkable capability of regeneration following injury. Satellite cells, the principal muscle stem cells, are responsible for this process. However, this regenerative capacity is reduced in muscular dystrophies or in old age: in both these situations, there is a net loss of muscle fibres. Promoting skeletal muscle muscle hypertrophy could therefore have potential applications for treating muscular dystrophies or sarcopenia. Here, we observed that muscles of dystrophic mdx nude host mice that had been acutely injured by myotoxin and grafted with a single myofibre derived from a normal donor mouse exhibited increased muscle area. Transplantation experiments revealed that the hypertrophic effect is mediated by the grafted fibre and does not require either an imposed injury to the host muscle, or the contribution of donor cells to the host muscle. These results suggest the presence of a crucial cross-talk between the donor fibre and the host muscle environment.
Highlights
Regeneration of skeletal muscle is primarily mediated by the resident adult muscle stem cells [1,2,3]
Single Donor Myofibres Grafted into BaCl2-treated Host Muscles do not Contribute to Muscle Regeneration, but do Cause Muscle Hypertrophy
As pre-modulation of host muscle is needed to promote donor satellite cell engraftment [45], and a single donor myofibre grafted in pre-irradiated host muscles generated donor-derived muscle [6], we wished to test if a different muscle modulation - BaCl2 that induces muscle degeneration and regeneration - could promote donor myofibre-mediated engraftment to the same extent
Summary
Regeneration of skeletal muscle is primarily mediated by the resident adult muscle stem cells [1,2,3]. Following muscle injury, they become activated, proliferate and differentiate to repair or replace myofibres and by self-renewing they functionally reconstitute the muscle stem cell pool [4,5]. Evidence of their enormous in vivo potential is given by the capacity of the few satellite cells associated with a single fibre [6], or a few hundred satellite cells isolated from fibres, to efficiently repair and regenerate host fibres after grafting in murine recipient muscles [6,7,8,9]. Donorderived muscle regeneration can be efficient only if the host satellite cell niche is preserved with concomitant functional impairment of the host satellite cells [9]
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