Stable release of BDNF from the fibroblast cell line NIH3T3 grown on silicone elastomers enhances survival of spiral ganglion cells in聽vitro and in聽vivo

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• 作者：Athanasia Warnecke^a ; ¹ ; ^{warnecke.athanasia@mh-hannover.de} ; Susanne Sasse^a ; ¹ ; Gentiana I. Wenzel^a ; Andrea Hoffmann^b ; ² ; Gerhard Gross^b ; Gerrit Paasche^a ; Verena Scheper^a ; Uta Reich^c ; Karl-Heinz Esser^d ; Thomas Lenarz^a ; Timo Stö ; ver^a ; ³ ; Kirsten Wissel^a ; ^{wissel.kirsten@mh-hannover.de}
• 关键词：BDNF ; brain-derived neurotrophic factor ; CI ; cochlea implant ; Dox ; doxycycline ; GFP ; green fluorescent protein ; SNHL ; sensorineural hearing loss ; IHC ; inner hair cells ; huMSC ; human mesenchymal stem cell ; SE ; silicone elastomer ; SEpl ; silicone elastomer s
• 刊名：Hearing Research
• 出版年：2012
• 期刊代码：111_03785955
• 类别：med
• 出版时间：July, 2012
• 卷：289
• 期：1-2
• 页码：86-97
• 文件大小：1636 K

摘要

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聽vitro and in聽vivo. An in聽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聽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聽vitro and in聽vivo. This therapeutic strategy - once transferred to cells suitable for clinical application - may improve CI performance.