Invited Session "Muscle stem cells and skeletal muscle plasticity"
Satellite cells and skeletal muscle regeneration; leads from cell culture and animal models
Harridge, S.
King's College London
Satellite cells are the muscle stems cells and have long believed to be necessary for muscle regeneration and repair as well as
involved in the hypertrophic process. However, it was not until relatively recently using lineage tracing studies on mice that it was
really possible to conclude that Pax7+ve satellite cells were indeed essential for muscle repair (Lepper et al. 2011, Sambasivan et al.
2011). Further use of transgenic models, in this case to ablate muscle fibroblasts, have also recently shown the need for these
connective tissue cells to act as a co-factor for optimal regeneration (Murphy et al. 2011).
In human muscle we are unable to undertake experiments using such techniques. However, cell culture techniques can be used to
study the behaviour of satellite cells - or ’myoblasts’ or ’muscle precursor cells’ as they are termed when located outside of their
anatomical niche. We have used human primary cell culture models to study the behaviour of skeletal muscle derived cells with a
particular focus on ageing. Our studies suggest that whilst a different phenotype can be created through replicative senescence in
culture, the potential for proliferation, fusion and differentiation is preserved in cells obtained from older people (Alsharidah et al.
2013). We have also studied the possibility that satellite cells might be diverted away from their myogenic lineage and may be the
origin of adipocytes contributing to the fibro-fatty phenotype characteristic of sarcopenia. We have developed cell sorting techniques
that allow us to purify populations of the two main adherent cell types from muscle biopsy samples - myoblasts (CD56+ve /
desmin+ve) and fibroblasts (TE7+ve). We have treated both of these cell types with physiological adipogenic cues (fatty acids) and
shown that myoblasts accumulate some lipid, but remain true to their myogenic lineage (Agley et al. 2013). In contrast, fibroblasts
accumulate significant amounts of lipid, extrude their fibroblast marker and express the transcription factors required for the
conversion of preadipocytes into to mature adipocytes (PPAR gamma and C/EBP/alpha). It seems from these experiments, that
myoblasts remain robustly myogenic for their role in muscle regeneration. By contrast fibroblasts, whilst having a supporting role in
satellite cell-mediated repair, also seem to act as a bi-potent stem cell population capable of transdifferentiation into adipocytes under
certain conditions.
8 июл 2024
