Muscle fibre proliferation and remodelling

Life Sciences 2007 (2007) Proc Life Sciences, SA136

Research Symposium: Muscle fibre proliferation and remodelling

L. Thornell1, M. Lindström1

1. IMB section for Anatomy, Umeå University, Umeå, Sweden.

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During the human life span the muscle mass undergo major changes. Furthermore the muscles are highly adaptive to usage; training might induce muscle hypertrophy and increased strength or increased endurance. The muscles have also a remarkable ability to recover after muscle damage. Of special importance is that the muscle fibres are not able to divide. The nuclei are post mitotic, thus the fibres are not either able to increase their myonuclei. The key structure related to muscle fibre proliferation and remodelling is the satellite cells. These cells, considered being a kind of stem cell, are located in between the muscle fibre plasma- and basement membranes. They are of crucial importance and are involved in both the adaptive and repair events of the muscle fibre. A number of factors affect and regulate the satellite cells. In the past electron microscopic analysis was needed to reveal the satellite cells, however nowadays a number of markers can be used to identify and quantify them using immunohistochemical methods and light microscopy. As the satellite cells seem to be heterogeneous within a muscle and between muscles there is no golden standard how to quantify them in situ. Furthermore other kind of stem cells be localized in the interstitium between muscle fibres and might act as additional candidates for muscle maintenance. Methodological considerations must therefore be taken into account when comparing results from different laboratories. The satellite cells can easily be investigated in cell cultures and their proliferative capacity can be estimated by their number of divisions they can perform and how their telomeres become shortened. One has also to remember that results from studies on animal muscles differ substantially from those on humans. During the years we have evaluated a number of markers to identify satellite cells. Our current view is that several markers on the same section are needed for a reliable estimation of satellite and stem cells in human muscles. Depending on if two or four markers are used we observe a marked difference in the number of satellite cells in relation to number of nuclei per fibre. Correlation of the number of SC in situ, to estimates from cell culture (number of divisions) and degree of telomere shortening have shown that a concomitant decrease of satellite cells and proliferative capacity occur in degenerative muscle disorders, during ageing and in highly exercised muscles. With regard to muscle fibre proliferation we have shown that there is a highly significant correlation between the number of muscle fiber nuclei in a cross section and the cross section area (Eriksson et al 2005). Related to the concept of nuclear domains i.e that one nucleus can govern a certain area of the cytoplasm with information for protein synthesis, the new nuclei are supposed to come from the satellite cells. Using strength trained elite athletes, some of which had also used anabolic steroids, we have achieved new information on possible hyperplasia of muscle fibres and on the aetiology and pathogenesis of so called split fibres (Eriksson et al 2006). Interestingly, previously anabolic steroid users had, although they stopped training, a significant higher amount of nuclei per fiber. This suggests that they would still have an advantage for increased protein synthesis if they would start training and compete again (Eriksson 2006). Upon inactivity, human as animal muscle fibres atrophy, however in humans we have not seen any loss in number of nuclei as are reported for animal muscles. Furthermore contrary to animal muscles, human muscle do not as easily become damaged upon exercise and muscle fibre necrosis are limited. Myofibrillar disorganisation as observed with electronmicroscopy, thought to represent damage and part of the cause to delayed onset muscle soreness, has recently be shown to be a process of myofibrillar remodelling (Yu et al 2004). The field of satellite and stem cells is growing fast and one can anticipate a dramatic increase of knowledge in the near future.



Where applicable, experiments conform with Society ethical requirements.

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