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Development of approaches to improve cell survival in myoblast transfer therapy

Academic Article
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Overview

authors

  • Qu, Z. Q.
  • Balkir, L.
  • van Deutekom, J. C. T.
  • Robbins, Paul D.
  • Pruchnic, R.
  • Huard, J.

publication date

  • September 1998

journal

  • Journal of Cell Biology  Journal

abstract

  • Myoblast transplantation has been extensively studied as a gene complementation approach for genetic diseases such as Duchenne Muscular Dystrophy. This approach has been found capable of delivering dystrophin, the product missing in Duchenne Muscular Dystrophy muscle, and leading to an increase of strength in the dystrophic muscle. This approach, however, has been hindered by numerous limitations, including immunological problems, and low spread and poor survival of the injected myoblasts. We have investigated whether antiinflammatory treatment and use of different populations of skeletal muscle-derived cells may circumvent the poor survival of the injected myoblasts after implantation. We have observed that different populations of muscle-derived cells can be isolated from skeletal muscle based on their desmin immunoreactivity and differentiation capacity. Moreover, these cells acted differently when injected into muscle: 95% of the injected cells in some populations died within 48 h, while others richer in desmin-positive cells survived entirely. Since pure myoblasts obtained from isolated myofibers and myoblast cell lines also displayed a poor survival rate of the injected cells, we have concluded that the differential survival of the populations of muscle-derived cells is not only attributable to their content in desmin-positive cells. We have observed that the origin of the myogenic cells may influence their survival in the injected muscle. Finally, we have observed that myoblasts genetically engineered to express an inhibitor of the inflammatory cytokine, IL-1, can improve the survival rate of the injected myoblasts. Our results suggest that selection of specific muscle-derived cell populations or the control of inflammation can be used as an approach to improve cell survival after both myoblast transplantation and the myoblast-mediated ex vivo gene transfer approach.

subject areas

  • Animals
  • Animals, Newborn
  • Cell Survival
  • Cells, Cultured
  • Desmin
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Immunohistochemistry
  • Inflammation
  • Mice
  • Mice, Inbred mdx
  • Muscle Proteins
  • Muscle, Skeletal
  • Receptors, Interleukin-1
  • Tissue Transplantation
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Research

keywords

  • adenovirus
  • inflammation gene transfer
  • muscle derived stem cells
  • myoblast transplantation
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Identity

International Standard Serial Number (ISSN)

  • 0021-9525

Digital Object Identifier (DOI)

  • 10.1083/jcb.142.5.1257

PubMed ID

  • 9732286
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Additional Document Info

start page

  • 1257

end page

  • 1267

volume

  • 142

issue

  • 5

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