Surgical access to the mammalian cochlea for cell-based therapies

Surgical access to the mammalian cochlea for cell-based therapies
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DOI:
10.1016/j.expneurol.2008.08.002
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发表时间:
2008-12-01
影响因子:
5.3
通讯作者:
Shepherd, Robert
Shepherd, Robert
中科院分区:
医学2区
文献类型:
--
作者:
Backhouse, Steven;Coleman, Bryony;Shepherd, Robert

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人工耳蜗术依赖于功能上可行的螺旋神经节神经元(SGN)--内耳的初级听觉神经元。基于细胞的疗法正在实验中使用,试图将SGN从耳聋引起的变性中拯救出来,或者产生新的神经元。这些疗法的成功将取决于外科技术的发展,这些技术旨在确保精确的细胞放置,同时将手术创伤、不良组织反应和细胞扩散降至最低。在24只正常成年豚鼠身上,我们评估了三种将细胞送入耳蜗内的手术方法:(I)鼓阶(ST)的耳蜗造口术;(Ii)通过局部的骨性螺旋板(RC)骨折直接进入Rosenthal管-SGN胞体的位置;(Iii)通过迷路手术入路(TL)直接进入听神经。队列中一半的人单独接受手术,另一半人接受手术并输送生物兼容微球,这些微球旨在为植入的细胞建模。在四周的生存期后,测量每个队列的炎症反应和SGN存活率,并确定微球的位置。我们观察到了三种手术入路的广泛差异,包括炎症组织反应的程度(TL>>RC>=ST)和SGN的存活率(ST>RC>>TL)。重要的是,微球在所有三种手术入路后都有效地保留在植入部位。直接进入罗森塔尔的管道提供了最有希望的手术入路。虽然这项技术必须进一步改进,以减少与手术相关的局部创伤。(C)2008 Elsevier Inc.保留所有权利。
Cochlear implants are dependent on functionally viable spiral ganglion neurons (SGNs) - the primary auditory neurons of the inner ear. Cell-based therapies are being used experimentally in an attempt to rescue SGNs from deafness-induced degeneration or to generate new neurons. The success of these therapies will be dependent oil the development of surgical techniques designed to ensure precise cell placement while minimizing Surgical trauma, adverse tissue reaction and cell dispersal. Using 24 normal adult guinea pigs we assessed three Surgical procedures for cell delivery into the cochlea: (i) a cochleostomy into the scala tympani (ST); (ii) direct access to Rosenthal's canal - the site of the SGN soma - via a localized fracture of the osseous spiral lamina (RC); and (iii) direct access to the auditory nerve via a translabyrinthine surgical approach (TL). Half the cohort had Surgery alone while the other half had Surgery combined with the delivery of biocompatible microspheres designed to model implanted cells. Following a four week Survival period the inflammatory response and SGN Survival were measured for each cohort and the location of microspheres were determined. We observed a wide variability across the three surgical approaches examined, including the extent of the inflammatory tissue response TL>>RC >= ST) and the survival of SGNs (ST>RC>>TL). Importantly, microspheres were effectively retained at the implant site after all three surgical approaches. Direct access to Rosenthal's canal offered the most promising surgical approach to the SGNs. although the technique Must be further refined to reduce the localized trauma associated with the procedure. (C) 2008 Elsevier Inc. All rights reserved.