Document Detail


Stable release of BDNF from the fibroblast cell line NIH3T3 grown on silicone elastomers enhances survival of spiral ganglion cells in vitro and in vivo.
MedLine Citation:
PMID:  22564255     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The treatment of choice for profound sensorineural hearing loss (SNHL) is direct electrical stimulation of spiral ganglion cells (SGC) via a cochlear implant (CI). The number and excitability of SGC seem to be critical for the success that can be achieved via CI treatment. However, SNHL is associated with degeneration of SGC. Long-term drug delivery to the inner ear for improving SGC survival may be achieved by functionalisation of CI electrodes with cells providing growth factors. Therefore, the capacity of brain-derived neurotrophic factor (BDNF)-secreting NIH3T3 cells grown on cylindrically shaped silicone elastomers (SE) to exert local and sustained neuroprotective effects was assessed in vitro and in vivo. An in vitro model to investigate adhesion and cell growth of lentivirally modified NIH3T3 cells synthesising BDNF on SE was established. The bioactivity of BDNF was characterised by co-cultivation of SGC with cell-coated SE. In addition, cell-coated SE were implanted into deafened guinea pigs. The recombinant NIH3T3 cells proliferated on silicone surfaces during 14 days of cultivation and expressed significantly increasing BDNF levels. Enhanced survival rates and neurite outgrowth of SGC demonstrated the bioactivity of BDNF in vitro. Implantation of SE with adhering BDNF-secreting NIH3T3 cells into the cochleae of systemically deafened guinea pigs induced a significant increase in SGC survival in comparison to SE without cell coating. Our data demonstrate a novel approach of cell-based long-term drug delivery to support SGC survival in vitro and in vivo. This therapeutic strategy - once transferred to cells suitable for clinical application - may improve CI performance.
Authors:
Athanasia Warnecke; Susanne Sasse; Gentiana I Wenzel; Andrea Hoffmann; Gerhard Gross; Gerrit Paasche; Verena Scheper; Uta Reich; Karl-Heinz Esser; Thomas Lenarz; Timo Stöver; Kirsten Wissel
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-28
Journal Detail:
Title:  Hearing research     Volume:  -     ISSN:  1878-5891     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-5-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7900445     Medline TA:  Hear Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Affiliation:
Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
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