PMID- 25088914
OWN - NLM
STAT- MEDLINE
DCOM- 20150608
LR  - 20201209
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 277
DP  - 2014 Sep 26
TI  - Development of a cell-based treatment for long-term neurotrophin expression and 
      spiral ganglion neuron survival.
PG  - 690-9
LID - S0306-4522(14)00617-4 [pii]
LID - 10.1016/j.neuroscience.2014.07.044 [doi]
AB  - 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.
CI  - Copyright (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Zanin, M P
AU  - Zanin MP
AD  - Bionics Institute, Melbourne, Australia.
FAU - Hellstrom, M
AU  - Hellstrom M
AD  - School of Anatomy, Physiology and Human Biology, The University of Western 
      Australia, Australia.
FAU - Shepherd, R K
AU  - Shepherd RK
AD  - Bionics Institute, Melbourne, Australia; Department of Medical Bionics, 
      University of Melbourne, Australia.
FAU - Harvey, A R
AU  - Harvey AR
AD  - School of Anatomy, Physiology and Human Biology, The University of Western 
      Australia, Australia.
FAU - Gillespie, L N
AU  - Gillespie LN
AD  - Bionics Institute, Melbourne, Australia; Department of Medical Bionics, 
      University of Melbourne, Australia. Electronic address: 
      lgillespie@bionicsinstitute.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140801
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NTF3 protein, human)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neurotrophin 3)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cell Culture Techniques
MH  - Cell Survival/physiology
MH  - Cell- and Tissue-Based Therapy/*methods
MH  - Coculture Techniques
MH  - Fibroblasts/*physiology
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Humans
MH  - Nerve Growth Factors/genetics/metabolism
MH  - Neurons/*physiology
MH  - Neurotrophin 3
MH  - Rats
MH  - Schwann Cells/physiology
MH  - Sciatic Nerve/physiology
MH  - Spiral Ganglion/*physiology
MH  - Transfection
OTO - NOTNLM
OT  - lentivirus
OT  - lipofection
OT  - neurotrophin
OT  - nucleofection
OT  - sensorineural hearing loss
OT  - spiral ganglion neuron
EDAT- 2014/08/05 06:00
MHDA- 2015/06/09 06:00
CRDT- 2014/08/05 06:00
PHST- 2014/03/12 00:00 [received]
PHST- 2014/06/13 00:00 [revised]
PHST- 2014/07/18 00:00 [accepted]
PHST- 2014/08/05 06:00 [entrez]
PHST- 2014/08/05 06:00 [pubmed]
PHST- 2015/06/09 06:00 [medline]
AID - S0306-4522(14)00617-4 [pii]
AID - 10.1016/j.neuroscience.2014.07.044 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Sep 26;277:690-9. doi: 10.1016/j.neuroscience.2014.07.044. 
      Epub 2014 Aug 1.