caa a22 4500 465820409 CHVBK 20180323112134.0 cr unu---uuuuu 170327e19901101xx s 000 0 eng 10.1007/BF01233096 doi (NATIONALLICENCE)springer-10.1007/BF01233096 Accelerated age-related decline in replicative life-span of Duchenne muscular dystrophy myoblasts: Implications for cell and gene therapy [Elektronische Daten] [Cecelia Webster, Helen Blau] An assessment of the replicative life-span of myoblasts is of fundamental importance in designing treatment strategies for Duchenne muscular dystrophy (DMD) based on cell or gene therapy. To ascertain myoblast life-span, or the total number of cell divisions of which a myoblast was capable, we serially passaged and counted the progeny of individual myoblasts until they senesced. We compared the life-span of myoblasts from eight DMD patients with controls: three individuals with no known neuromuscular disease, three DMD carriers, and three patients with other muscle degenerative diseases. A decline in replicative capacity was observed with increasing donor age, which was markedly accelerated for DMD relative to control myoblasts. The average myoblast from a 5-year-old control was capable of 56 doublings, or a potential yield of approximately 1017 cells per cell. By contrast, at 2 years of age, the typical age at clinical onset, only 6% of DMD myoblasts had a life-span of 50 doublings in tissue culture, and by age 7 DMD myoblasts capable of 10 doublings were rare. Our results suggest that the myoblasts (satellite cells) of even the youngest DMD patients have undergone extensive division in an attempt to regenerate degenerating myofibers. These findings have implications for therapeutic intervention in DMD involving genetic engineering and myoblast implantation. Plenum Publishing Corporation, 1990 Webster Cecelia Department of Pharmacology, Stanford University School of Medicine, 94305-5332, Stanford, California aut Blau Helen Department of Pharmacology, Stanford University School of Medicine, 94305-5332, Stanford, California aut Somatic Cell and Molecular Genetics Kluwer Academic Publishers-Plenum Publishers 16/6(1990-11-01), 557-565 0740-7750 16:6<557 1990 16 11188 https://doi.org/10.1007/BF01233096 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01233096 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Webster Cecelia Department of Pharmacology, Stanford University School of Medicine, 94305-5332, Stanford, California aut NATIONALLICENCE 700 1- Blau Helen Department of Pharmacology, Stanford University School of Medicine, 94305-5332, Stanford, California aut NATIONALLICENCE 773 0- Somatic Cell and Molecular Genetics Kluwer Academic Publishers-Plenum Publishers 16/6(1990-11-01), 557-565 0740-7750 16:6<557 1990 16 11188 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer