Restoration of auditory evoked responses by human ES-cell-derived otic progenitors.
Restoration of auditory evoked responses by human ES-cell-derived otic progenitors.
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DOI：
10.1038/nature11415
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发表时间：
2012-10-11
期刊：
影响因子：
64.8
通讯作者：
Rivolta, Marcelo N.
中科院分区：
文献类型：
--
作者：
Chen, Wei;Jongkamonwiwat, Nopporn;Abbas, Leila;Eshtan, Sarah Jacob;Johnson, Stuart L.;Kuhn, Stephanie;Milo, Marta;Thurlow, Johanna K.;Andrews, Peter W.;Marcotti, Walter;Moore, Harry D.;Rivolta, Marcelo N.
耳聋是一种在世界范围内高度流行的疾病，主要由感觉毛细胞及其相关的螺旋神经节神经元(SGN)的丧失引起。在所有形式的耳聋中，听神经病是一个特别令人担忧的问题。这种情况主要由SGN的损害和毛细胞的相对保存来定义，是相当大比例的听力障碍患者的原因。虽然毛细胞的丢失可以通过人工耳蜗部分避免，但感觉神经元的丢失没有常规的治疗方法，因为不良的神经支配限制了植入物的预期性能。使用干细胞修复受损的感觉回路是一种潜在的治疗策略。在这里，我们提出了一种方案，利用耳道胎盘的初始规范中涉及的信号来诱导人类胚胎干细胞(HESCs)分化。我们获得了两种类型的耳祖细胞，它们能够在体外分化为毛细胞样细胞和表现出预期电生理特性的听觉神经元。此外，当移植到听神经病模型中时，耳神经前体细胞植入、分化并显著提高听觉诱发反应(ABR)阈值。这些结果应该会刺激进一步研究以细胞为基础的耳聋治疗方法的发展。
Deafness is a condition with a high prevalence worldwide, produced primarily by the loss of the sensory hair cells and their associated spiral ganglion neurons (SGNs). Of all the forms of deafness, auditory neuropathy is of a particular concern. This condition, defined primarily by damage to the SGNs with relative preservation of the hair cells , is responsible for a substantial proportion of patients with hearing impairment . While the loss of hair cells can be circumvented partially by a cochlear implant, no routine treatment is available for sensory neuron loss since poor innervation limits the prospective performance of an implant . Using stem cells to recover the damaged sensory circuitry is a potential therapeutic strategy. Here, we present a protocol to induce differentiation from human embryonic stem cells (hESCs) using signals involved in the initial specification of the otic placode. We obtained two types of otic progenitors able to differentiate in vitro into hair cell-like cells and auditory neurons that display expected electrophysiological properties. Moreover, when transplanted into an auditory neuropathy model, otic neuroprogenitors engraft, differentiate and significantly improve auditory evoked response (ABR) thresholds. These results should stimulate further research into the development of a cell-based therapy for deafness.
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影响因子：
64.5
作者：
Oshima K;Shin K;Diensthuber M;Peng AW;Ricci AJ;Heller S
通讯作者：
Heller S
影响因子：
4.6
作者：
Alvarez, Y;Alonso, MT;Schimmang, T
通讯作者：
Schimmang, T
DOI：
10.1002/neu.20310
发表时间：
2006-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Corrales, C. Eduardo;Pan, Luying;Edge, Albert S. B.
通讯作者：
Edge, Albert S. B.
影响因子：
2.8
作者：
Rask-Andersen, H;Boström, M;Lindholm, D
通讯作者：
Lindholm, D
DOI：
10.1073/pnas.0408239102
发表时间：
2005-03-29
影响因子：
11.1
作者：
Kondo, T;Johnson, SA;Hashino, E
通讯作者：
Hashino, E