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J. Cell Biol.,
Volume 142, Number 5, September 7, 1998 1257-1267
§
* Department of Orthopedic Surgery, Musculoskeletal Research Center, University of Pittsburgh and Children's Hospital of
Pittsburgh, Pittsburgh, Pennsylvania 15261; 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.
Department of Human Genetics, and § Department of Molecular Genetics and
Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15261
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