Invited Session "Muscle stem cells and skeletal muscle plasticity"

Muscle stem cells in skeletal muscle atrophy and hypertrophy
Vardijk, L.B.
Maastricht University

The regenerative capacity of skeletal muscle tissue depends on a pool of undifferentiated myogenic precursor cells, known as
satellite cells. In adult muscle, satellite cells typically remain quiescent in their niche between the basal lamina and the sarcolemma.
However, in response to injury and/or exercise stimuli, satellite cells become activated. After proliferation, satellite cells can fuse
together with existing myofibers (donating their nucleus to the fiber), or return to quiescence to replenish the resident pool of muscle
stem cells by selfrenewal. Changes in satellite cell content as well as satellite cell function have been suggested to represent key
factors in regulating the skeletal muscle adaptive response to various stimuli, such as exercise, but also in response to different
(pathological) conditions, such as aging and/or disuse.
At present, much of the knowledge on satellite cell biology and their role in skeletal muscle plasticity stems from extensive in vitro and
animal work. Yet, translation of this knowledge toward the exact role of satellite cells in skeletal muscle adaptation in a physiological,
human, in vivo situation is challenging and inconsistencies are quite common. For example, it appears evident from a number of
human studies, that skeletal muscle hypertrophy in response to resistance training in both the young and old is more efficient (i.e.
more robust) when satellite cell induced incorporation of new myonuclei is achieved. This is in line with the myonuclear domain
theory, suggesting that myonuclei can only control a finite volume of cytoplasm, and fusion of new nuclei facilitates extensive muscle
fiber hypertrophy. However, the actual requirement of satellite cells and, as such, new myonuclei, for attaining extensive hypertrophy
has recently been challenged in specific experimental animal models. Likewise, the myonuclear domain theory would suggest that
muscle atrophy may be associated with a reduction in myonuclear content. However, current literature remains equivocal as to
whether myonuclei and/or satellite cells are lost with different models of muscle atrophy. As such, it remains to be determined to what
extent potential changes in satellite cell and/or myonuclear content play a role in the extent of atrophy on one hand, and the capacity
for skeletal muscle regrowth on the other hand. In this symposium, the role of muscle stem cells in skeletal muscle atrophy and
hypertrophy will be further discussed. Though the focus will be on human work, evidence from animal experiments will be used to
further broaden the discussion in this evolving field of science.