Somatic Cell and Molecular Genetics

, Volume 16, Issue 6, pp 557–565 | Cite as

Accelerated age-related decline in replicative life-span of Duchenne muscular dystrophy myoblasts: Implications for cell and gene therapy

  • Cecelia Webster
  • Helen M. Blau
Article

Abstract

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.

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Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Cecelia Webster
    • 1
  • Helen M. Blau
    • 1
  1. 1.Department of PharmacologyStanford University School of MedicineStanford

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