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Review
. 2023 Dec 29;25(1):512.
doi: 10.3390/ijms25010512.

Regulation of Satellite Cells Functions during Skeletal Muscle Regeneration: A Critical Step in Physiological and Pathological Conditions

Giorgia Careccia  1 , Laura Mangiavini  2   3 , Federica Cirillo  4   5
Affiliations
Review

Regulation of Satellite Cells Functions during Skeletal Muscle Regeneration: A Critical Step in Physiological and Pathological Conditions

Giorgia Careccia et al. Int J Mol Sci. .

Abstract

Skeletal muscle regeneration is a complex process involving the generation of new myofibers after trauma, competitive physical activity, or disease. In this context, adult skeletal muscle stem cells, also known as satellite cells (SCs), play a crucial role in regulating muscle tissue homeostasis and activating regeneration. Alterations in their number or function have been associated with various pathological conditions. The main factors involved in the dysregulation of SCs' activity are inflammation, oxidative stress, and fibrosis. This review critically summarizes the current knowledge on the role of SCs in skeletal muscle regeneration. It examines the changes in the activity of SCs in three of the most common and severe muscle disorders: sarcopenia, muscular dystrophy, and cancer cachexia. Understanding the molecular mechanisms involved in their dysregulations is essential for improving current treatments, such as exercise, and developing personalized approaches to reactivate SCs.

Keywords: cancer cachexia; muscular dystrophy; sarcopenia; satellite cells; skeletal muscle regeneration.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of sarcopenia. Sarcopenic skeletal muscle is characterized by the loss of myofibers, which are replaced by fibrous and fatty tissue. The number of SCs decreases in sarcopenia. The tissue is more heavily infiltrated with inflammatory cells (lymphocytes and macrophages). Fast fibers (light pink) are severely impacted by mass loss, while slow fibers are not affected (dark pink). The neuromuscular connections are impaired. On the right side, the SCs’ dysfunctions are caused by senescence-associated factors (higher concentration of cytokines and myostatin; decrease in IGF1), which stimulate senescence and the senescence-associated secretory phenotype.
Figure 2
Figure 2
Schematic representation of muscular dystrophy. Dystrophic muscles are characterized by cycles of degeneration and regeneration, which, over time, lead to the loss of myofibers with an accumulation of mostly fibrotic tissue. The fast fibers (light pink) are the most affected by the cycles of regeneration and regeneration, causing an abnormal morphology of the neuromuscular junctions, while slow fibers are not affected (dark pink). High infiltration of inflammatory cells (lymphocytes and macrophages) leads to an increase in the number of SCs, which, however, show a dysfunctional phenotype. The dysfunctions observed in the SCs are triggered by extracellular factors (cytokines) but also by intracellular defects (lack of dystrophin) that lead to a disruption of asymmetric division as well as senescence and changes in the myogenic signature towards a fibrotic and immunological signature.
Figure 3
Figure 3
Schematic representation of cancer cachexia. A cachectic muscle is characterized by a decrease in muscle mass due to changes in metabolism but also by changes in the function of the SCs. The skeletal muscle shows a reduced number of infiltrating cells (lymphocytes and macrophages), although it is degenerated in places. The fast fibers (light pink) are most severely affected and show a high degree of denervation, while slow fibers are not affected (dark pink). The main change is a state of hyper-quiescence of the SCs, which leads to overexpression of PAX7 via the NF-κB and myostatin pathways.
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