TY - JOUR
T1 - IGF-1 gene transfer into denervated rat laryngeal muscle
AU - Flint, Paul W.
AU - Shiotani, Akihiro
AU - O'Malley, Bert W.
PY - 1999/3
Y1 - 1999/3
N2 - Objectives: To demonstrate gene transfer in rat laryngeal muscle using a reporter gene, β-galactosidase, and a muscle-specific expression system containing the human IGF-1 (hIGF-1) gene sequence and to investigate the myotrophic and neurotrophic effects of hIGF-1 gene transfer in denervated rat laryngeal muscle. Methods: In 8 adult rats, a polyvinyl-based formulation containing β-galactosidase DNA was injected into denervated thyroarytenoid muscle. Twelve animals were similarly administered a polyvinyl-based formulation containing a muscle-specific expression system and hIGF-1 DNA. Twelve animals were injected with isotonic sodium chloride solution, and all animals survived for 1 month. The production of β-galactosidase and hIGF-1 was detected using immunohistochemical techniques. The effects of hIGF-1 on motor endplates and nerve sprouting were assessed using cholinesterase or silver staining and immunostaining for growth-associated protein (GAP-43). Results: β-Galactosidase was detected in 7 of 8 animals by immunostaining, X-gal histochemical staining, or both. In frozen section specimens, hIGE-1 immunoreactivity was positive in 3 of 8 animals. In sequential sections, GAP- 43 was localized to areas of hIGF-1 expression in 2 of the 3 hIGF-1-positive specimens. Increased nerve sprouting and motor endplate contact occurred in 2 of 4 animals treated with hIGF-1. Conclusions: Gene transfer into laryngeal muscle was demonstrated using a polyvinyl-based formulation containing a muscle-specific gene expression system. Preliminary findings indicate a positive effect on motor endplates, nerve sprouting, and the expression of GAP-43 in animals treated with the hIGF-1 vector. This study establishes a foundation for investigating hIGF-1 gene transfer as a novel treatment of laryngeal paralysis. Further studies are necessary to quantify myotrophic and neurotrophic effects and to establish therapeutic benefit.
AB - Objectives: To demonstrate gene transfer in rat laryngeal muscle using a reporter gene, β-galactosidase, and a muscle-specific expression system containing the human IGF-1 (hIGF-1) gene sequence and to investigate the myotrophic and neurotrophic effects of hIGF-1 gene transfer in denervated rat laryngeal muscle. Methods: In 8 adult rats, a polyvinyl-based formulation containing β-galactosidase DNA was injected into denervated thyroarytenoid muscle. Twelve animals were similarly administered a polyvinyl-based formulation containing a muscle-specific expression system and hIGF-1 DNA. Twelve animals were injected with isotonic sodium chloride solution, and all animals survived for 1 month. The production of β-galactosidase and hIGF-1 was detected using immunohistochemical techniques. The effects of hIGF-1 on motor endplates and nerve sprouting were assessed using cholinesterase or silver staining and immunostaining for growth-associated protein (GAP-43). Results: β-Galactosidase was detected in 7 of 8 animals by immunostaining, X-gal histochemical staining, or both. In frozen section specimens, hIGE-1 immunoreactivity was positive in 3 of 8 animals. In sequential sections, GAP- 43 was localized to areas of hIGF-1 expression in 2 of the 3 hIGF-1-positive specimens. Increased nerve sprouting and motor endplate contact occurred in 2 of 4 animals treated with hIGF-1. Conclusions: Gene transfer into laryngeal muscle was demonstrated using a polyvinyl-based formulation containing a muscle-specific gene expression system. Preliminary findings indicate a positive effect on motor endplates, nerve sprouting, and the expression of GAP-43 in animals treated with the hIGF-1 vector. This study establishes a foundation for investigating hIGF-1 gene transfer as a novel treatment of laryngeal paralysis. Further studies are necessary to quantify myotrophic and neurotrophic effects and to establish therapeutic benefit.
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U2 - 10.1001/archotol.125.3.274
DO - 10.1001/archotol.125.3.274
M3 - Article
C2 - 10190798
AN - SCOPUS:0033040584
SN - 0886-4470
VL - 125
SP - 274
EP - 279
JO - Archives of Otolaryngology - Head and Neck Surgery
JF - Archives of Otolaryngology - Head and Neck Surgery
IS - 3
ER -