Muscular Dystrophy Stem Cell Treatment

Canadian researchers looking at the molecular regulation of muscle stem cell function have now differentiated between two subsets of muscle satellite cells, those which are capable of repopulating the satellite cell pool and those which actually give rise to new muscle cells (myoblasts). The two sets of muscle stem cells express the transcription factor Pax7 which is required for satellite cells to remain viable and also for the formation of precursor muscle cells (myogenic precursor cells). Rudnicki (et al, 2009) observed that in vivo approximately 10% of the satellite cells only express Pax7 and have never expressed Myf5, a transcription factor essential in the determination of cells as myogenic cells. What this means is that there is a population of muscle satellite cells that has incredible therapeutic potential for treating degenerative muscle disease.


UPDATE May 2012: University of Minnesota Researchers find way to treat muscular dystrophy in mice, using human skin cells turned into muscle cells.

Duchenne Muscular Dystrophy

Muscle degeneration can occur for a number of reasons including nerve damage and resulting muscle wasting, acute trauma, infection, autoimmune disease, and genetic mutation. Patients with Duchenne Muscular Dystrophy (DMD) experience progressive degeneration of skeletal muscle which becomes fatal due to a mutation of dystrophin. Researchers investigating Duchenne muscular dystrophy have discovered that dystrophin deficiency in a specific mouse model does not cause the same degree of muscle degeneration, and the mice retain their regenerative capacity to avoid the same fate as human patients (Sacco, et al, 2010). The explanation for this difference between the laboratory mice and human patients given by Sacco, et al, is that the mice have a larger reserve of functional muscle stem cells, whereas the human DMD patients experience a progressive loss of these stem cells and, therefore, their ability to regenerate muscle tissue.

Stem Cell Transplants for Muscle Regeneration

In a different mouse model where the mice have shortened telomeres in the muscle stem cells the effects of muscular dystrophy are significantly more pronounced and progress rapidly with age. Transplanting functional muscle stem cells would then, theoretically, allow for better regeneration of skeletal muscle and postpone or prevent the wasting observed with usual disease progression.

Muscle satellite cells are not the only stem cells being researched for autologous stem cell transplant as recent research by Yang (et al, 2010) located dental stem cells which could differentiate into dystrophin-producing multi-nucleated muscle cells. These stem cells found in dental pulp may then be stored for later stem cell therapy in muscular dystrophy characterized by dystrophin deficiency.

Clinical Trials for Muscular Dystrophy

Clinical trials using stem cell therapy for muscular dystrophy are likely to occur soon based on both anecdotal reports from stem cell clinics in Germany and China and experimental work on animals in the laboratory. Two of the most common forms of muscular dystrophy are Duchenne and Becker which affects 1 in 3500-5000 boys in the US each year (Center for Disease Control and Prevention, 2005). Muscular dystrophy can affect both men and women however, but does tend to be familial. Symptoms include muscle wasting, skeletal weakness, gatrointestinal sluggishness, and cardiovascular problems along with possible cognitive irregularities such as mood swings, and memory problems. Some patients also experience problems with their eyes, skin, and the endocrine system. Stem cell researchers found that foetal stem cells called mesangioblasts had the potential for use in correcting limb-girdle muscular dystrophy, a specific form of the disease (Sampaolesi, et al, 2003). The inability to carry out human trials at this time prevented verification of this as a stem cell treatment for muscular dystrophy.

Related Topics – Muscle Stem Cells and Satellite Cell Activity

References

Yang, R., Chen, M., Lee, C.H., Yoon, R., Lal, S., et al., (2010), Clones of Ectopic Stem Cells in the Regeneration of Muscle Defects In Vivo, PLoS ONE 5(10): e13547. doi:10.1371/journal.pone.0013547

Cossu, G., Bianco, P., (2009), Mesoangioblasts — vascular progenitors for extravascular mesodermal tissues, Current Opinion in Genetics & Development, Volume 13, Issue 5, October 2003, Pages 537-542

Tanaka, K.K., Hall, J.K., Troy, A.A., Cornelison, D.D.W., Majka, S.M., Olwin, B.B., (2003), Syndecan-4-Expressing Muscle Progenitor Cells in the SP Engraft as Satellite Cells during Muscle Regeneration, Cell Stem Cell, Volume 4, Issue 3, 6 March 2009, Pages 217-225

Fontana, S., Cohn, R.D., (2009), SP-litting the Satellite Niche to Repopulate Muscle, Volume 4, Issue 3, 6 March 2009, Pages 194-195

Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, July 27, 2005