title: Muscle-targeted hydrodynamic gene introduction of insulin-like growth factor-1 using polyplex nanomicelle to treat peripheral nerve injury.
abstract: The recovery of neurologic function after peripheral nerve injury often remains incomplete because of the prolonged reinnervation process, which leads to skeletal muscle atrophy and articular contracture from disuse over time. To rescue the skeletal muscle and promote functional recovery, insulin-like growth factor-1 (IGF-1), a potent myogenic factor, was introduced into the muscle by hydrodynamic injection of IGF-1-expressing plasmid DNA using a biocompatible nonviral gene carrier, a polyplex nanomicelle. In a mouse model of sciatic nerve injury, the introduction of IGF-1 into the skeletal muscle of the paralyzed limb effectively alleviated a decrease in muscle weight compared with that in untreated control mice. Histologic analysis of the muscle revealed the IGF-1-expressing plasmid DNA (pDNA) to have a myogenic effect, inducing muscle hypertrophy with the upregulation of the myogenic regulatory factors, myogenin and MyoD. The evaluation of motor function by walking track analysis revealed that the group that received the hydrodynamic injection of IGF-1-expressing pDNA using the polyplex nanomicelle had significantly early recovery of motor function compared with groups receiving negative control pDNA and untreated controls. Early recovery of sensation in the distal area of sciatic nerve injury was also induced by the introduction of IGF-1-expressing pDNA, presumably because of the effect of secreted IGF-1 protein in the vicinity of the injured sciatic nerve exerting a synergistic effect with muscle hypertrophy, inducing a more favorable prognosis. This approach of introducing IGF-1 into skeletal muscle is promising for the treatment of peripheral nerve injury by promoting early motor function recovery.
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nagata
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan. Electronic address: itaka-ort@umin.net.
authors.forename: Keiji
authors.initials: K
authors.lastname: Itaka
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Baba
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Japan. Electronic address: kataoka@bmw.t.u-tokyo.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D057446:Hydrodynamics; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000235:genetics*; D008807:Mice, Inbred BALB C; D008823:Micelles; D009043:Motor Activity / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D018006:Myogenic Regulatory Factors / Q000235:genetics; D049329:Nanostructures / Q000737:chemistry*; D009929:Organ Size / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D010957:Plasmids; D012584:Sciatic Nerve / Q000293:injuries
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D008823:Micelles; D018006:Myogenic Regulatory Factors; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D004247:DNA
keywords: Gene delivery; Hydrodynamic injection; Insulin-like growth factor-1 (IGF-1); Muscle atrophy; Peripheral nerve injury; Polyplex nanomicelle