- Satellite cells
Satellite cells are small mononuclear
progenitor cells with virtually nocytoplasm found in maturemuscle . They are found sandwiched between thebasement membrane andsarcolemma (cell membrane) of individual muscle fibres, and can be difficult to distinguish from the sub-sarcolemmal nuclei of the fibres. Satellite cells are able to differentiate and fuse to augment existingmuscle fibres and to form new fibres. These cells represent the oldest known adultstem cell niche, and are involved in the normal growth of muscle, as well as regeneration following injury ordisease .In undamaged muscle, the majority of satellite cells are "quiescent"; they neither differentiate nor undergo cell division. In response to mechanical strain, satellite cells become "activated". Activated satellite cells initially proliferate as skeletal
myoblast s before undergoing myogenic differentiation.Genetic markers of satellite cells
Satellite cells express a number of distinctive
genetic markers . Current thinking is that all satellite cell expressPax7 andPax3 [cite journal | author = Relaix F, Rocancourt D, Mansouri A, Buckingham M | title = A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. | journal = Nature | volume = 435 | issue = 7044 | pages = 898–9 | year = 2005 | pmid = 15843801 | doi = 10.1038/nature03594]Activated satellite cells express myogenic transcription factors, such as
Myf5 andMyoD . They also begin expressing muscle-specific filament proteins such asdesmin 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. Studies rely almost exclusively on
Flow Cytometry and Flourescence Activated Cell Sorting (FACS) analysis, which gives no information about cell lineage or behaviour. As such, the satellite cell niche and is relatively ill-defined and it is likely that it consists of multiple sub-populations.Function in muscular repair
When muscle cells undergo injury, quiescent satellite cells are released from beneath the
basement membrane . They become activated and re-enter thecell cycle . These dividing cells are known as the "transit amplifying pool" before undergoing myogenic differentiation to form new (post-mitotic) myotubes. 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. Fibroblasts within the muscle deposit scar tissue, which can impair muscle function, and is a significant part of the pathology of
muscular dystrophies .Plasticity and Therapeutic Applications
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 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 andhematopoietic stem cells have all been shown to be able to contribute to muscle repair in a similar manner to the endogenous satellite cell. 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. Particularly successful recently has been the delivery ofmesoangioblast cells into theGolden Retriever dog model ofDuchenne muscular dystrophy , which effectively cured the disease [cite journal | author = Sampaolesi M, Cossu, G. et al | title = Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs | journal = Nature | volume = 444 | issue = 7119 | pages = 574–9 | year = 2006 | pmid = 17108972 | doi = 10.1038/nature05282] .Regulation
Little is known of the regulation of satellite cells. Whilst together
Pax3 andPax7 currently form the definitive satellite markers, Pax genes are notoriously poor transcriptional activators. The dynamics of activation and quiesence and the induction of the myogenic program through the "myogenic regulatory factors",Myf5 ,MyoD ,myogenin , andMRF4 remains to be determined.There is some research indicating that satellite cells are negatively regulated by a protein called
myostatin . Increased levels of myostatin up-regulate acyclin-dependent kinase inhibitor called p21 and thereby induce the differentiation of satellite cells. [cite journal | author = McCroskery S, Thomas M, Maxwell L, Sharma M, Kambadur R | title = Myostatin negatively regulates satellite cell activation and self-renewal. | journal = J Cell Biol | volume = 162 | issue = 6 | pages = 1135–47 | year = 2003 | pmid = 12963705 | doi = 10.1083/jcb.200207056]References
External links
* [http://www.neuro.wustl.edu/neuromuscular/mother/myogenesis.html#satcell Image at neuro.wustl.edu]
* [http://www.brown.edu/Courses/BI0032/adltstem/sc.htm Overview at brown.edu]
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