Auditory hair cell explant co-cultures promote the differentiation of stem cells into bipolar neurons

Auditory hair cell explant co-cultures promote the differentiation of stem cells into bipolar neurons
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DOI:
10.1016/j.yexcr.2006.10.010
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发表时间:
2007-01-15
影响因子:
3.7
通讯作者:
Shepherd, R. K.
Shepherd, R. K.
中科院分区:
医学3区
文献类型:
--
作者:
Coleman, B.;Fallon, J. B.;Shepherd, R. K.

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听觉神经元是人工耳蜗的目标神经元,在感音神经性听力损失后会退化。这项研究的目标是引导胚胎干细胞(SC)分化为双极听觉神经元,可用于替代失聪的哺乳动物耳蜗中退化的神经元。成功替换听觉神经元可能会改善人工耳蜗植入者的临床结果。我们检查了两种有或没有神经营养支持的产后听觉共培养模型,以了解它们指导小鼠胚胎 SC 分化为特征性双极听觉神经元的潜力。通过与从出生后第 5 天的大鼠分离的听觉神经元或毛细胞外植体共培养,可以促进 SC 分化为神经元样细胞。最成功的组合是毛细胞外植体与整个胚状体的共培养,这导致神经丝阳性的神经元样细胞数量显着增加。虽然在移植研究开始之前对这些分化细胞的进一步表征至关重要,但这些数据说明了出生后毛细胞外植体共培养的有效性,为 SC 定向分化为听觉神经元谱系提供了有价值的分子线索。 (c) 2006 Elsevier Inc. 保留所有权利。
Auditory neurons, the target neurons of the cochlear implant, degenerate following a sensorineural hearing loss. The goal of this research is to direct the differentiation of embryonic stem cells (SCs) into bipolar auditory neurons that can be used to replace degenerating neurons in the deafened mammalian cochlea. Successful replacement of auditory neurons is likely to result in improved clinical outcomes for cochlear implant recipients. We examined two post-natal auditory co-culture models with and without neurotrophic support, for their potential to direct the differentiation of mouse embryonic SCs into characteristic, bipolar, auditory neurons. The differentiation of SCs into neuron-like cells was facilitated by co-culture with auditory neurons or hair cell explants, isolated from post-natal day five rats. The most successful combination was the co-culture of hair cell explants with whole embryoid bodies, which resulted in significantly greater numbers of neurofilament-positive, neuron-like cells. While further characterization of these differentiated cells will be essential before transplantation studies commence, these data illustrate the effectiveness of post-natal hair cell explant co-culture, at providing valuable molecular cues for directed differentiation of SCs towards an auditory neuron lineage. (c) 2006 Elsevier Inc. All rights reserved.