Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion
Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion
复制标题
DOI：
10.1089/scd.2013.0274
复制
发表时间：
2014-03-01
影响因子：
4
通讯作者：
Goldstein, Bradley J.
中科院分区：
文献类型：
--
作者：
Bas, Esperanza;Van De Water, Thomas R.;Goldstein, Bradley J.
内耳感觉毛细胞或螺旋神经节神经元的丧失会导致耳聋，影响数百万人。目前，还没有有效的治疗方法来修复人类的内耳感觉结构。人工耳蜗植入可以恢复输入，但前提是听觉神经元保持完好。开发基于干细胞的耳聋治疗方法的努力已经取得了进展，最引人注目的是利用了胚胎来源的细胞。为了绕过胚胎或诱导的多能干细胞可能阻碍转化到临床应用的局限性，我们试图利用另一种细胞来源。在这里，我们展示了从鼻腔组织中获得的成人间充质样干细胞(MSCs)可以修复实验性损伤的新生大鼠耳蜗培养中螺旋神经节的丢失。干细胞移植到庆大霉素损伤的器官培养中，协调螺旋神经节神经元群体的恢复，包括直接的神经元分化和对内源性细胞的继发性作用。作为一种生理测试，移植到受损螺旋神经节的鼻MSC来源的细胞对红外激光刺激的反应与典型的可兴奋细胞一致。在干细胞治疗的同时，增加典型的Wnt/β-Catenin通路的药理激活剂，促进了强大的神经元分化。用于内耳组织修复的有效的成人自体细胞来源的可用性应该有助于将基于细胞的策略转化为临床。
A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic.