Inducible nerve growth factor delivery for peripheral nerve regeneration in vivo. 2010

Thomas Scholz, and Jason M Rogers, and Alisa Krichevsky, and Sanjay Dhar, and Gregory R D Evans
Orange, Calif. From the Aesthetic and Plastic Surgery Institute, University of California, Irvine.

BACKGROUND HEK-293 cells can be genetically modified to release and regulate nerve growth factor (NGF) in vitro. The aim of this study was to evaluate the impact of this NGF delivery system on peripheral nerve regeneration in vivo. METHODS HEK-293 cells were transfected with an ecdysone receptor, NGF cDNA, and herpes simplex virus-thymidine kinase suicide vector. NGF production is induced by ponasterone A and stopped by ganciclovir. A 13-mm sciatic nerve gap was bridged with Silastic conduits in 120 nude rats, and transfected HEK-293 cells were added, induced, and boostered to secrete bioactive NGF. RESULTS The induction of the cell line and additional booster with ponasterone A demonstrated significantly higher levels of bioactive NGF, enhanced macroscopic nerve growth, improved functional recovery, and histologic regeneration when compared with control groups after 7, 14, and 21 days, and 2 and 4 months. The treatment with ganciclovir resulted in suppression of the NGF production and decreased functional and histologic outcomes. CONCLUSIONS Transfected HEK-293 cells can be regulated to inducibly produce bioactive NGF in vivo over prolonged periods. This tissue-engineered nerve construct including the NGF delivery system is able to improve peripheral nerve regeneration and functional recovery and appears to be superior to nerve isografts.

UI MeSH Term Description Entries
D009416 Nerve Regeneration Renewal or physiological repair of damaged nerve tissue. Nerve Tissue Regeneration,Nervous Tissue Regeneration,Neural Tissue Regeneration,Nerve Tissue Regenerations,Nervous Tissue Regenerations,Neural Tissue Regenerations,Regeneration, Nerve,Regeneration, Nerve Tissue,Regeneration, Nervous Tissue,Regeneration, Neural Tissue,Tissue Regeneration, Nerve,Tissue Regeneration, Nervous,Tissue Regeneration, Neural
D009431 Neural Conduction The propagation of the NERVE IMPULSE along the nerve away from the site of an excitation stimulus. Nerve Conduction,Conduction, Nerve,Conduction, Neural,Conductions, Nerve,Conductions, Neural,Nerve Conductions,Neural Conductions
D010525 Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Endoneurium,Epineurium,Perineurium,Endoneuriums,Epineuriums,Nerve, Peripheral,Nerves, Peripheral,Perineuriums,Peripheral Nerve
D011923 Rats, Nude A mutant strain of Rattus norvegicus without a thymus and with depressed or absent T-cell function. This strain of rats may have a small amount of hair at times, but then lose it. Athymic Rats,Nude Rats,Rats, Athymic,Athymic Rat,Nude Rat,Rat, Athymic,Rat, Nude
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004441 Ecdysterone A steroid hormone that regulates the processes of MOLTING or ecdysis in insects. Ecdysterone is the 20-hydroxylated ECDYSONE. 20-Hydroxyecdysone,Beta-Ecdysone,Crustecdysone,20 Hydroxyecdysone,Beta Ecdysone
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D001369 Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Axon

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