Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by widespread muscle damage that invariably leads to paralysis and death. There is currently no therapy for this disease. Here we report that a subpopulation of circulating cells expressing AC133, a well-characterized marker of hematopoietic stem cells, also expresses early myogenic markers. Freshly isolated, circulating AC133 + cells were induced to undergo myogenesis when cocultured with myogenic cells or exposed to Wnt-producing cells in vitro and when delivered in vivo through the arterial circulation or directly into the muscles of transgenic scid/mdx mice (which allow survival of human cells). Injected cells also localized under the basal lamina of host muscle fibers and expressed satellite cell markers such as M-cadherin and MYF5. Furthermore, functional tests of injected muscles revealed a substantial recovery of force after treatment. As these cells can be isolated from the blood, manipulated in vitro, and delivered through the circulation, they represent a possible tool for future cell therapy applications in DMD disease or other muscular dystrophies.

Duchenne muscular dystrophy (DMD) is a hereditary disease caused by mutations that disrupt the dystrophin mRNA reading frame. In some cases, forced exclusion (skipping) of a single exon can restore the reading frame, giving rise to a shorter, but still functional, protein. In this study, we constructed lentiviral vectors expressing antisense oligonucleotides in order to induce an efficient exon skipping and to correct the initial frameshift caused by the DMD deletion of CD133+ stem cells. The intramuscular and intra-arterial delivery of genetically corrected CD133 expressing myogenic progenitors isolated from the blood and muscle of DMD patients results in a significant recovery of muscle morphology, function, and dystrophin expression in scid/mdx mice. These data demonstrate that autologous engrafting of blood or muscle-derived CD133+ cells, previously genetically modified to reexpress a functional dystrophin, represents a promising approach for DMD.

Neurodegenerative diseases (NDDs) originate from a loss of neurons in the central nervous system and are severely debilitating. The incidence of NDDs increases with age, and they are expected to become more common due to extended life expectancy. Because no cure is available, these diseases have become a major challenge in neurobiology. The increasing relevance of microRNAs (miRNAs) in biology has prompted investigation into their possible involvement in neurodegeneration in order to identify new therapeutic targets. The idea of using miRNAs as therapeutic targets is not far from realization, but important issues need to be addressed before moving into the clinics. Here, we review what is known about the involvement of miRNAs in the pathogenesis of NDDs. We also report the miRNA expression levels in peripheral tissues of patients affected by NDDs in order to evaluate their application as biomarkers of disease. Finally, discrepancies, innovations, and the effectiveness of collected data will be elucidated and discussed.