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.

No abstract

With age, skeletal muscle mitochondria lose their oxidative capacity and their ability to respond to energy demand. These phenomena can lead to a reduction in skeletal muscle oxygen consumption, atrophy, and increased risk of developing age-related diseases such as sarcopenia. Whether age-derived changes in mitochondrial function correspond to structural changes in the mitochondrial reticulum remains unknown. PURPOSE: Investigate age-related changes in mitochondrial morphology and function using primary skeletal muscle cells derived from healthy young and old men. METHODS: Primary skeletal muscle progenitor cells (SkM) derived from the Rectus abdominis muscle of healthy active 18-19-year-old men (SkM Young), and 66-69-year-old men (SkM Old) were obtained from Cook MyoSite Inc. (Pittsburgh, PA). The mitochondrial network was analyzed in live cells using confocal microscopy. Oxygen Consumption Rate (OCR) was measured in intact cells using extracellular flux assays and a Seahorse analyzer (Agilent Technologies

As skeletal muscle fibres mostly express a single myosin isoform, they are a potential source of pure myosin isoforms. A technique is described that allows extraction and identification of pure myosin isoforms from single fibres, and testing of such myosins in an in vitro motility assay (IVMA). The results show that the extraction procedure does not alter myosin function and support the view that single fibres are reliable sources of purified myosin isoforms for IVMA.

No abstract