Stem and Progenitor Cells in Skeletal Muscle Development, Maintenance, and Therapy

Abstract

Satellite cells are dormant progenitors located at the periphery of skeletal myofibers that can be triggered to proliferate for both self-renewal and differentiation into myogenic cells. In addition to anatomic location, satellite cells are typified by markers such as M-cadherin, Pax7, Myf5, and neural cell adhesion molecule-1. The Pax3 and Pax7 transcription factors play essential roles in the early specification, migration, and myogenic differentiation of satellite cells. In addition to muscle-committed satellite cells, multi-lineage stem cells encountered in embryonic, as well as adult, tissues exhibit myogenic potential in experimental conditions. These multi-lineage stem cells include side-population cells, muscle-derived stem cells (MDSCs), and mesoangioblasts. Although the ontogenic derivation, identity, and localization of these non-conventional myogenic cells remain elusive, recent results suggest their ultimate origin in blood vessel walls. Indeed, purified pericytes and endothelium-related cells demonstrate high myogenic potential in culture and in vivo. Allogeneic myoblasts transplanted into Duchenne muscular dystrophy (DMD) patients have been, in early trials, largely inefficient owing to immune rejection, rapid death, and limited intramuscular migration--all obstacles that are now being alleviated, at least in part, by more efficient immunosuppression and escalated cell doses. As an alternative to myoblast transplantation, stem cells such as mesoangioblasts and CD133+ progenitors administered through blood circulation have recently shown great potential to regenerate dystrophic muscle.

Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

“…(80) Muscle progenitor cells have been characterized as expressing the transcription factor Pax7 and are positive for the cluster differentiation markers CD34, CD44, CD56, and CD146. (45) The high expression of different mesodermal and myogenic markers in the SB-OG cell population also was observed when skeletal myocytes were isolated from different tissues of the body. (45) Therefore, this study confirms the presence of an early mesoderm stem cell population that has a multipotential differentiation ability.…”

“…2C, D). Furthermore, NCAM þ cells were found to stain positive for the myogenic markers desmin þ (80% to 90%), ASMA þ (30% to 40%), and SERCA1 þ (SR-1, 19% AE 3%) (45) (Fig. 2D) and were negative for paired box transcription factor 7 positive (Pax7 þ , 25% AE 4%) (46) (Fig.…”

Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells

“…Nevertheless, in the last ten years, evidence has accumulated that other progenitors can contribute to skeletal muscle regeneration either by direct fusion or by entering the satellite cell pool [6][7][8][27][28][29][30][31][32][33][34][35][36] . When identified, the anatomical niche of these cells has been often associated with blood vessels (endothelial cells, pericytes and also haematopoietic cells).…”

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

“…The study by Mu and Li (2010) showed that incubation of primary myoblasts or C2C12 immortalised myoblasts with a transient and small concentration of TGF-β can lead to the expression of more primitive markers, Pax7 and Sca-1 [52]. However, in the aforementioned study the authors identify the expression of Pax7 and Sca-1 as an indication of reversion to an MSC phenotype, although Pax7 is more commonly used as an indicator of satellite cell phenotype, and Sca-1 has also been identified as a marker of muscle cell progenitors [54]. Therefore, it may be more likely that the presence of inflammatory factors such as TGF-β could lead to a reversion of myoblasts to an earlier muscle progenitor/satellite cell type, which may possess an osteochondrogenic potential.…”