Development of a cell-based treatment for long-term neurotrophin expression and spiral ganglion neuron survival.

Autor: Zanin MP; Bionics Institute, Melbourne, Australia., Hellström M; School of Anatomy, Physiology and Human Biology, The University of Western Australia, Australia., Shepherd RK; Bionics Institute, Melbourne, Australia; Department of Medical Bionics, University of Melbourne, Australia., Harvey AR; School of Anatomy, Physiology and Human Biology, The University of Western Australia, Australia., Gillespie LN; Bionics Institute, Melbourne, Australia; Department of Medical Bionics, University of Melbourne, Australia. Electronic address: lgillespie@bionicsinstitute.org.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2014 Sep 26; Vol. 277, pp. 690-9. Date of Electronic Publication: 2014 Aug 01.
DOI: 10.1016/j.neuroscience.2014.07.044
Abstrakt: Spiral ganglion neurons (SGNs), the target cells of the cochlear implant, undergo gradual degeneration following loss of the sensory epithelium in deafness. The preservation of a viable population of SGNs in deafness can be achieved in animal models with exogenous application of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3. For translation into clinical application, a suitable delivery strategy that provides ongoing neurotrophic support and promotes long-term SGN survival is required. Cell-based neurotrophin treatment has the potential to meet the specific requirements for clinical application, and we have previously reported that Schwann cells genetically modified to express BDNF can support SGN survival in deafness for 4 weeks. This study aimed to investigate various parameters important for the development of a long-term cell-based neurotrophin treatment to support SGN survival. Specifically, we investigated different (i) cell types, (ii) gene transfer methods and (iii) neurotrophins, in order to determine which variables may provide long-term neurotrophin expression and which, therefore, may be the most effective for supporting long-term SGN survival in vivo. We found that fibroblasts that were nucleofected to express BDNF provided the most sustained neurotrophin expression, with ongoing BDNF expression for at least 30 weeks. In addition, the secreted neurotrophin was biologically active and elicited survival effects on SGNs in vitro. Nucleofected fibroblasts may therefore represent a method for safe, long-term delivery of neurotrophins to the deafened cochlea to support SGN survival in deafness.
(Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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