Duchenne muscular dystrophy and extraocular muscle: a potential sparing mechanism with therapeutic implications.
2009-10
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Duchenne muscular dystrophy and extraocular muscle: a potential sparing mechanism with therapeutic implications.
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2009-10
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This project investigates the role of extraocular muscle (EOM) progenitor cells in sparing the muscles from pathology associated with Duchenne Muscular Dystrophy (DMD). Mouse models of muscular dystrophy and wild type mice were analyzed by flow cytometry and cell culture for the size, heterogeneity and functional characteristics of stem and satellite cell populations of EOM and limb muscles. EOM have a 5-fold increase in progenitor cells compared with limb muscles. Additionally, an enriched population of cells expressing the stem cell marker CD34 but no other typical stem or differentiation markers (Sca-1, CD45, CD31, pax-7, m-cadherin) exists in the EOM. We refer to this population as EOMCD34 cells. The EOMCD34 cells are present in developing muscle, but only maintained in adult EOM, surviving in very aged animals. The EOMCD34 cells are also present in EOM of DMD model animals, but not their limb muscles. EOMCD34 cells are resistant to apoptosis and proliferate in vivo. Finally, these cells are capable of forming myotubes in vitro. The EOMCD34 cells may represent a primitive stem cell population, which is capable of maintaining life-long pools of myogenic precursor cells. Since EOM continuously remodel throughout life, unlike other skeletal muscle, it is logical that the proliferative potential of their precursor cells is enhanced. Since one proposed mechanism of DMD muscle destruction is exhaustion of the reparative progenitor cells, the EOMCD34 cells might prove useful for myoblast transplant therapies for DMD.
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University of Minnesota Ph.D. dissertation. November 2009. Major: Neuroscience. Advisor: Linda McLoon, Ph.D., 1 computer file (PDF); v, 118 pages.
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Kallestad, Kristen Marie. (2009). Duchenne muscular dystrophy and extraocular muscle: a potential sparing mechanism with therapeutic implications.. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/57808.
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