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  • Title: Gene complementation using myoblast transfer into fetal muscle.
    Author: Sopper MM, Hauschka SD, Hoffman E, Ontell M.
    Journal: Gene Ther; 1994 Mar; 1(2):108-13. PubMed ID: 7584065.
    Abstract:
    Gene complementation by myoblast transfer into neonatal or adult muscle has been proposed as a therapy for primary myopathies as well as to augment non-muscle gene products that may be diminished in the adult circulation. This paper describes a technique whereby myoblasts have been injected into limb muscles of normal and dystrophin-deficient (mdx) fetal mice (during the period of active myotube formation and prior to the development of the host's immune competence) without significantly interfering with fetal viability or further maturation. More mosaic myofibers (myofibers containing both host- and donor-derived myonuclei) appear to result from these transfers than have been reported following myoblast transfer into neonatal muscle or adult muscle. The small size of the fetal hosts' muscles and the lack of well-defined connective tissue septa facilitate migration of donor myoblasts into muscle groups distal to the injection site. The use of donor myoblasts derived from a tetraploid variant of a mouse myogenic cell line (MM14) provides a convenient and permanent cytological marker for the recognition of donor myoblasts and donor-derived myonuclei. When MM14 myoblasts are injected into mdx fetuses, whose muscles lack dystrophin, mosaic myofibers contain sufficient dystrophin to be visualized with routine immunohistochemical techniques. The myoblast transfer system, using fetal hosts, described in this study will facilitate the evaluation of myoblasts as vectors to overcome genetic deficiencies that may be manifested during fetal development.
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