Satellite cellThese cells represent the oldest known adult stem cell niche, and are involved in the normal growth of muscle, as well as regeneration following injury or disease. In undamaged muscle, the majority of satellite cells are quiescent; they neither differentiate nor undergo cell division. They also begin expressing muscle-specific filament proteins such as desmin as they differentiate. It should be noted that the field of satellite cell biology suffers from the same technical difficulties as other stem cell fields.
They become activated and re-enter the cell cycle. These dividing cells are known as the transit amplifying pool before undergoing myogenic differentiation to form new (post-mitotic) myotubes.
They are found sandwiched between the basement membrane and sarcolemma (cell membrane) of individual muscle fibres, and can be difficult to distinguish from the sub-sarcolemmal nuclei of the fibres. Increased levels of myostatin up-regulate a cyclin-dependent kinase inhibitor called p21 and thereby induce the differentiation of satellite cells. DAP: Sarcoglycan (SGCA, SGCB, SGCD, SGCE, SGCG, SGCZ) · Dystroglycan Dystrophin · Dystrobrevin (A, B) · Syntrophin (A, B1, B2, G1, G2) · Syncoilin · Dysbindin · Synemin/desmuslin Myofilament (thin filament/actin, thick filament/myosin, elastic filament/titin, nebulin) Tropomyosin .
As such systemic treatments or even the treatment of an entire muscle in this way is not possible. However, other cells in the body such as pericytes and hematopoietic stem cells have all been shown to be able to contribute to muscle repair in a similar manner to the endogenous satellite cell.
Studies rely almost exclusively on Flow cytometry and Fluorescence Activated Cell Sorting (FACS) analysis, which gives no information about cell lineage or behaviour. Fibroblasts within the muscle deposit scar tissue, which can impair muscle function, and is a significant part of the pathology of muscular dystrophies. Upon minimal stimulation, satellite cells in vitro or in vivo will undergo a myogenic differentiation program. Unfortunately, it seems that transplanted satellite cells have a limited capacity for migration, and are only able to regenerate muscle in the region of the delivery site.
As such, the satellite cell niche and is relatively ill-defined and it is likely that it consists of multiple sub-populations. When muscle cells undergo injury, quiescent satellite cells are released from beneath the basement membrane. Current thinking is that all satellite cells express PAX7 and PAX3 Activated satellite cells express myogenic transcription factors, such as Myf5 and MyoD.
Activated satellite cells initially proliferate as skeletal myoblasts before undergoing myogenic differentiation. Satellite cells express a number of distinctive genetic markers. Whilst together PAX3 and PAX7 currently form the definitive satellite markers, Pax genes are notoriously poor transcriptional activators.
In response to mechanical strain, satellite cells become activated. The dynamics of activation and quiesence and the induction of the myogenic program through the myogenic regulatory factors, Myf5, MyoD, myogenin, and MRF4 remains to be determined. There is some research indicating that satellite cells are negatively regulated by a protein called myostatin.
The advantage of using these cell types for therapy in muscle diseases is that they can be systemically delivered, autonomously migrating to the site of injury. However, the sample size used was relatively small and the study has since been criticized for a lack of appropriate controls for the use of immunosupressive drugs. Little is known of the regulation of satellite cells.
Particularly successful recently has been the delivery of mesoangioblast cells into the Golden Retriever dog model of Duchenne muscular dystrophy, which effectively cured the disease. There is also evidence suggesting that these cells are capable of fusing with existing myofibres to facilitate growth and repair. The process of muscle regeneration involves considerable remodeling of extracellular matrix and, where extensive damage occurs, is incomplete.
Satellite cells are able to differentiate and fuse to augment existing muscle fibres and to form new fibres. Satellite cells are small mononuclear progenitor cells with virtually no cytoplasm found in mature muscle.