Duchenne muscular dystrophy : isolation of CD133-expressing myogenic progenitors from blood and muscle of DMD patients

Duchenne Muscular Dystrophy is a lethal X-linked recessive disorder caused by deficiency of the protein dystrophin. It is the most common muscular dystrophy in children (with an incidence of 1 in 3500 male live births), presenting in early childhood (first onset at 3/4 years) and it is characterized by progressive and profound loss of muscle strength, followed by exhaustion of muscular regenerative capacity, fibrosis, and eventually disruption of the muscle tissue architecture. This condition leads to death into the second second/third decade of the patient life. In the last decade, stem cells have received much attention because of their potential use in cell-based therapies for human diseases. At the beginning, the expression of CD133 antigen was seen only in the haematopoietic system-derived CD34+ stem cells. Few years after, a similar population was also identified in muscle. Since 2004 when CD133+ stem cells were discovered, several works showed the pattern of expression of these cells, their ability to differentiate in vitro into specific lineage such as endothelial and muscular, their capacity to migrate from vessels after transplantation into animal model of muscular dystrophy and to participate to muscular regeneration rather than to replenish satellite cells pool. Moreover, CD133+ isolated from blood- and muscle of DMD patients were treated with lentiviral vectors to skip the mutated region of dystrophin in order to express a shorter dystrophin mRNA transcripts showing the correct coding reading frame. Transplanted into dystrophic animal models, these cells were able to ameliorate their pathological phenotype. This approach of using exon-skipping for the expression of human dystrophin within the DMD CD133+ cells should allow the use of the patient’s own stem cells, thus minimizing the risk of immunological graft rejection. According to these characteristic, blood- and muscle-derived CD133+ were considered feasible for a possible clinical usage in transplantation experiments.