Taura Akiko, Ohnishi Hiroe, Ochi Shohei, Ebisu Fumi, Nakagawa Takayuki, Ito Juichi
BMC Neurosci. 2014 Nov 6;15:121. doi: 10.1186/s12868-014-0121-7.
Hair cells are important for maintaining our sense of hearing and balance. However, they are difficult to regenerate in mammals once they are lost. Clarification of the molecular mechanisms underlying inner ear disorders is also impeded by the anatomical limitation of experimental access to the human inner ear. Therefore, the generation of hair cells, possibly from induced pluripotent stem (iPS) cells, is important for regenerative therapy and studies of inner ear diseases.
We generated hair cells from mouse iPS cells using an established stepwise induction protocol. First, iPS cells were differentiated into the ectodermal lineage by floating culture. Next, they were treated with basic fibroblast growth factor to induce otic progenitor cells. Finally, the cells were co-cultured with three kinds of mouse utricle tissues: stromal tissue, stromal tissue + sensory epithelium, and the extracellular matrix of stromal tissue. Hair cell-like cells were successfully generated from iPS cells using mouse utricle stromal tissues. However, no hair cell-like cells with hair bundle-like structures were formed using other tissues.
Hair cell-like cells were induced from mouse iPS cells using mouse utricle stromal tissues. Certain soluble factors from mouse utricle stromal cells might be important for induction of hair cells from iPS cells.
毛细胞对于维持我们的听觉和平衡感至关重要。然而，一旦它们在哺乳动物体内丢失，就很难再生。对内耳疾病潜在分子机制的阐明也因对人类内耳进行实验的解剖学限制而受阻。因此，有可能从诱导多能干细胞（iPS细胞）生成毛细胞，这对于再生治疗和内耳疾病研究具有重要意义。
我们使用既定的逐步诱导方案从小鼠iPS细胞中生成了毛细胞。首先，通过悬浮培养将iPS细胞分化为外胚层谱系。接下来，用碱性成纤维细胞生长因子处理它们以诱导耳祖细胞。最后，将这些细胞与三种小鼠椭圆囊组织共同培养：基质组织、基质组织 + 感觉上皮以及基质组织的细胞外基质。使用小鼠椭圆囊基质组织从小鼠iPS细胞中成功生成了毛细胞样细胞。然而，使用其他组织未形成具有毛束样结构的毛细胞样细胞。
使用小鼠椭圆囊基质组织从小鼠iPS细胞中诱导出了毛细胞样细胞。来自小鼠椭圆囊基质细胞的某些可溶性因子可能对于从小鼠iPS细胞诱导毛细胞很重要。
