Skeletal muscle regeneration after insulin-like growth factor I gene transfer by recombinant Sendai virus vector.
We scrutinized the applicability and efficacy of Sendai virus (SeV) vectors expressing either LacZ or human insulin-like growth factor-I (hIGF-I) in gene transfer into skeletal muscle. Seven days after the intramuscular injection of LacZ/SeV X-gal labeled myofibers were demonstrated in rat anterior tibialis muscle with/without bupivacaine treatment and the transgene expression persisted up to 1 month after injection. Recombinant hIGF-I was detected as a major protein species in culture supernatants of a neonatal rat myoblast cell line L6 and thus induced the cells to undergo myogenetic differentiation. The introduction of hIGF-I/SeV into the muscle showed a significant increase in regenerating and split myofibers which were indicative of hypertrophy, and also an increase in the total number of myofibers, in comparison to that seen in the LacZ/SeV-treated control muscle. These results demonstrate that SeV achieves high-level transgene expression in skeletal muscle, and that hIGF-I gene transfer using SeV vector may therefore have great potential in the treatment of neuromuscular disorders.
Shiotani
A
A
Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.
Fukumura
M
M
Maeda
M
M
Hou
X
X
Inoue
M
M
Kanamori
T
T
Komaba
S
S
Washizawa
K
K
Fujikawa
S
S
Yamamoto
T
T
Kadono
C
C
Watabe
K
K
Fukuda
H
H
Saito
K
K
Sakai
Y
Y
Nagai
Y
Y
Kanzaki
J
J
Hasegawa
M
M
D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006614:Hindlimb; D006801:Humans; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D007763:Lac Operon; D008297:Male; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000502:physiology*; D009468:Neuromuscular Diseases / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000032:analysis; D012038:Regeneration; D018108:Respirovirus / Q000235:genetics; D014162:Transfection / Q000379:methods; D019076:Transgenes
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I