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内耳干细胞衍生的饲养层促进羊水干细胞向功能性神经元的定向分化。

Inner ear stem cells derived feeder layer promote directional differentiation of amniotic fluid stem cells into functional neurons.

作者信息

Zong Ling, Chen Kaitian, Zhou Wei, Jiang Di, Sun Liang, Zhang Xuemei, Jiang Hongyan

机构信息

Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-Sen University and Institute of Otorhinolaryngology, Sun Yat-Sen University, Guangzhou 510080, PR China.

Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-Sen University and Institute of Otorhinolaryngology, Sun Yat-Sen University, Guangzhou 510080, PR China; Department of Otorhinolaryngology, Dongguan People's Hospital, Dongguan 523059, PR China.

出版信息

Hear Res. 2014 Oct;316:57-64. doi: 10.1016/j.heares.2014.07.012. Epub 2014 Aug 11.

Abstract

Intact spiral ganglion neurons are required for cochlear implantation or conventional hearing amplification as an intervention for sensorineural hearing loss. Treatment strategies to replace the loss of spiral ganglion neurons are needed. Recent reports have suggested that amniotic fluid-derived stem cells are capable of differentiating into neuron-like cells in response to cytokines and are not tumorigenic. Amniotic fluid stem cells represent a potential resource for cellular therapy of neural deafness due to spiral ganglion pathology. However, the directional differentiation of amniotic fluid stem cells is undetermined in the absence of cytokines and the consequence of inner ear supporting cells from the mouse cochlea organ of Corti on the differentiation of amniotic fluid stem cells remains to be defined. In an effort to circumvent these limitations, we investigated the effect of inner ear stem cells derived feeder layer on amniotic fluid stem cells differentiation in vitro. An inner ear stem cells derived feeder layer direct contact system was established to induce differentiation of amniotic fluid stem cells. Our results showed that inner ear stem cells derived feeder layer successfully promoted directional differentiation of amniotic fluid stem cells into neurons with characteristics of functionality. Furthermore, we showed that Wnt signaling may play an essential role in triggering neurogenesis. These findings indicate the potential use of inner ear stem cells derived feeder layer as a nerve-regenerative scaffold. A reliable and effective amniotic fluid stem cell differentiation support structure provided by inner ear stem cells derived feeder layer should contribute to efforts to translate cell-based strategies to the clinic.

摘要

完整的螺旋神经节神经元是人工耳蜗植入或传统听力放大作为感音神经性听力损失干预措施所必需的。需要有替代螺旋神经节神经元损失的治疗策略。最近的报告表明,羊水来源的干细胞能够在细胞因子的作用下分化为神经元样细胞,且不会形成肿瘤。羊水干细胞是因螺旋神经节病变导致神经性耳聋细胞治疗的潜在资源。然而,在没有细胞因子的情况下,羊水干细胞的定向分化尚未确定,来自小鼠柯蒂氏器内耳支持细胞对羊水干细胞分化的影响仍有待明确。为了克服这些限制,我们研究了内耳干细胞来源的饲养层对羊水干细胞体外分化的影响。建立了内耳干细胞来源的饲养层直接接触系统以诱导羊水干细胞分化。我们的结果表明,内耳干细胞来源的饲养层成功促进了羊水干细胞向具有功能特性的神经元的定向分化。此外,我们表明Wnt信号通路可能在触发神经发生中起重要作用。这些发现表明内耳干细胞来源的饲养层有可能用作神经再生支架。内耳干细胞来源的饲养层提供的可靠且有效的羊水干细胞分化支持结构应有助于将基于细胞的策略转化到临床的努力。

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