PMID- 18304740 OWN - NLM STAT- MEDLINE DCOM- 20080721 LR - 20211020 IS - 0306-4522 (Print) IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 152 IP - 3 DP - 2008 Mar 27 TI - Schwann cells genetically modified to express neurotrophins promote spiral ganglion neuron survival in vitro. PG - 821-8 LID - 10.1016/j.neuroscience.2007.11.057 [doi] AB - The intracochlear infusion of neurotrophic factors via a mini-osmotic pump has been shown to prevent deafness-induced spiral ganglion neuron (SGN) degeneration; however, the use of pumps may increase the incidence of infection within the cochlea, making this technique unsuitable for neurotrophin administration in a clinical setting. Cell- and gene-based therapies are potential therapeutic options. This study investigated whether Schwann cells which were genetically modified to over-express the neurotrophins brain-derived neurotrophic factor (BDNF) or neurotrophin 3 (Ntf3, formerly NT-3) could support SGN survival in an in vitro model of deafness. Co-culture of either BDNF over-expressing Schwann cells or Ntf3 over-expressing Schwann cells with SGNs from early postnatal rats significantly enhanced neuronal survival in comparison to both control Schwann cells and conventional recombinant neurotrophin proteins. Transplantation of neurotrophin over-expressing Schwann cells into the cochlea may provide an alternative means of delivering neurotrophic factors to the deaf cochlea for therapeutic purposes. FAU - Pettingill, L N AU - Pettingill LN AD - The Bionic Ear Institute, 384 Albert Street, East Melbourne, Australia 3002. lpettingill@bionicear.org FAU - Minter, R L AU - Minter RL FAU - Shepherd, R K AU - Shepherd RK LA - eng GR - N01 DC031005/DC/NIDCD NIH HHS/United States GR - N01-DC-3-1005/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080101 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) SB - IM MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cell Communication/genetics MH - Cell Survival/*genetics MH - Cells, Cultured MH - Coculture Techniques MH - Gene Expression Regulation/genetics MH - Genetic Therapy/methods MH - Hearing Loss, Sensorineural/genetics/prevention & control/therapy MH - Nerve Degeneration/genetics/prevention & control/therapy MH - Nerve Growth Factors/*genetics/metabolism MH - Neurons, Afferent/cytology/*metabolism MH - Neurotrophin 3/genetics/metabolism MH - Rats MH - Rats, Wistar MH - Schwann Cells/cytology/*metabolism MH - Spiral Ganglion/cytology/*metabolism PMC - PMC2726277 MID - NIHMS46172 EDAT- 2008/02/29 09:00 MHDA- 2008/07/22 09:00 PMCR- 2009/08/13 CRDT- 2008/02/29 09:00 PHST- 2007/08/30 00:00 [received] PHST- 2007/11/26 00:00 [revised] PHST- 2008/01/09 00:00 [accepted] PHST- 2008/02/29 09:00 [pubmed] PHST- 2008/07/22 09:00 [medline] PHST- 2008/02/29 09:00 [entrez] PHST- 2009/08/13 00:00 [pmc-release] AID - S0306-4522(07)01528-X [pii] AID - 10.1016/j.neuroscience.2007.11.057 [doi] PST - ppublish SO - Neuroscience. 2008 Mar 27;152(3):821-8. doi: 10.1016/j.neuroscience.2007.11.057. Epub 2008 Jan 1.