Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell. 2010 May 14;141(4):704-16. doi: 10.1016/j.cell.2010.03.035.
Mechanosensitive sensory hair cells are the linchpin of our senses of hearing and balance. The inability of the mammalian inner ear to regenerate lost hair cells is the major reason for the permanence of hearing loss and certain balance disorders. Here, we present a stepwise guidance protocol starting with mouse embryonic stem and induced pluripotent stem cells, which were directed toward becoming ectoderm capable of responding to otic-inducing growth factors. The resulting otic progenitor cells were subjected to varying differentiation conditions, one of which promoted the organization of the cells into epithelial clusters displaying hair cell-like cells with stereociliary bundles. Bundle-bearing cells in these clusters responded to mechanical stimulation with currents that were reminiscent of immature hair cell transduction currents.
机械敏感感觉毛细胞是我们听觉和平衡感的关键。哺乳动物内耳无法再生丧失的毛细胞,这是听力损失和某些平衡障碍永久性的主要原因。在这里,我们提供了一个从小鼠胚胎干细胞和诱导多能干细胞开始的逐步指导方案,这些细胞被定向成为能够响应耳诱导生长因子的外胚层。所得的耳前体细胞被置于不同的分化条件下,其中一种条件促进了细胞组织成具有纤毛束的毛细胞样细胞的上皮簇。这些簇中的带束细胞对机械刺激的反应产生的电流类似于未成熟的毛细胞转导电流。