Development of approaches to improve cell survival in myoblast transfer therapy

Zhuqing Qu, Levent Balkir, Judith C.T. Van Deutekom, Paul D. Robbins, Ryan Pruchnic, Johnny Huard

Research output: Contribution to journalArticlepeer-review

390 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1257-1267
Number of pages11
JournalJournal of Cell Biology
Volume142
Issue number5
DOIs
StatePublished - Sep 7 1998
Externally publishedYes

Keywords

  • Adenovirus
  • Gene transfer
  • Inflammation
  • Muscle derived stem cells
  • Myoblast transplantation

Fingerprint

Dive into the research topics of 'Development of approaches to improve cell survival in myoblast transfer therapy'. Together they form a unique fingerprint.

Cite this