Schwann cells genetically modified to express neurotrophins promote spiral ganglion neuron survival in vitro.
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.
Pettingill
L N
LN
The Bionic Ear Institute, 384 Albert Street, East Melbourne, Australia 3002. lpettingill@bionicear.org
Minter
R L
RL
Shepherd
R K
RK
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005786:Gene Expression Regulation / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000517:prevention & control / Q000628:therapy; D009410:Nerve Degeneration / Q000235:genetics / Q000517:prevention & control / Q000628:therapy; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D013136:Spiral Ganglion / Q000166:cytology / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3