Schwann cells genetically modified to express neurotrophins promote spiral ganglion neuron survival in vitro

被引:66
作者
Pettingill, L. N. [1 ,2 ]
Minter, R. L. [2 ]
Shepherd, R. K. [1 ,2 ]
机构
[1] Bion Ear Inst, Melbourne, Vic 3002, Australia
[2] Univ Melbourne, Dept Otolaryngol, Melbourne, Vic 3002, Australia
关键词
auditory; ex vivo gene transfer; BDNF; Ntf3;
D O I
10.1016/j.neuroscience.2007.11.057
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:821 / 828
页数:8
相关论文
共 72 条
[31]   Lack of efficacy of antibiotic-impregnated shunt systems in preventing shunt infections in children [J].
Kan, Peter ;
Kestle, John .
CHILDS NERVOUS SYSTEM, 2007, 23 (07) :773-777
[32]   In vitro and in vivo assessment of the ability of adeno-associated virus-brain-derived neurotrophic factor to enhance spiral ganglion cell survival following ototoxic insult [J].
Lalwani, AK ;
Han, JJ ;
Castelein, CM ;
Carvalho, GJ ;
Mhatre, AN .
LARYNGOSCOPE, 2002, 112 (08) :1325-1334
[33]   COCHLEAR PATHOLOGY OF LONG-TERM NEOMYCIN INDUCED DEAFNESS IN CATS [J].
LEAKE, PA ;
HRADEK, GT .
HEARING RESEARCH, 1988, 33 (01) :11-34
[34]   Neurotrophin secretion: current facts and future prospects [J].
Lessmann, V ;
Gottmann, K ;
Malcangio, M .
PROGRESS IN NEUROBIOLOGY, 2003, 69 (05) :341-374
[35]   The neurotrophins act synergistically with LIF and members of the TGF-β superfamily to promote the survival of spiral ganglia neurons in vitro [J].
Marzella, PL ;
Gillespie, LN ;
Clark, GM ;
Bartlett, PF ;
Kilpatrick, TJ .
HEARING RESEARCH, 1999, 138 (1-2) :73-80
[36]   Schwann cells genetically modified to secrete human BDNF promote enhanced axonal regrowth across transected adult rat spinal cord [J].
Menei, P ;
Montero-Menei, C ;
Whittemore, SR ;
Bunge, RP ;
Bunge, MB .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1998, 10 (02) :607-621
[37]   Neurotrophins can enhance spiral ganglion cell survival after inner hair cell loss [J].
Miller, JM ;
Chi, DH ;
OKeeffe, LJ ;
Kruszka, P ;
Raphael, Y ;
Altschuler, RA .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 1997, 15 (4-5) :631-643
[38]  
Mirsky R, 1999, BRAIN PATHOL, V9, P293
[39]   A disorganized innervation of the inner ear persists in the absence of ErbB2 [J].
Morris, Jacqueline K. ;
Maklad, Adel ;
Hansen, Laura A. ;
Feng, Feng ;
Sorensen, Christian ;
Lee, Kuo-Fen ;
Macklin, Wendy B. ;
Fritzsch, Bernd .
BRAIN RESEARCH, 2006, 1091 :186-199
[40]   The use of intrathecal baclofen pump implants in children and adolescents: safety and complications in 200 consecutive cases [J].
Motta, Francesco ;
Buonaguro, Vincenzo ;
Stignani, Cecilia .
JOURNAL OF NEUROSURGERY, 2007, 107 (01) :32-35