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首页> 外文期刊>BioResearch open access. >Directing Human Induced Pluripotent Stem Cells into a Neurosensory Lineage for Auditory Neuron Replacement
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Directing Human Induced Pluripotent Stem Cells into a Neurosensory Lineage for Auditory Neuron Replacement

机译：指导人类诱导多能干细胞进入听觉神经元置换的神经感觉谱系。

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Emerging therapies for sensorineural hearing loss include replacing damaged auditory neurons (ANs) using stem cells. Ultimately, it is important that these replacement cells can be patient-matched to avoid immunorejection. As human induced pluripotent stem cells (hiPSCs) can be obtained directly from the patient, they offer an opportunity to generate patient-matched neurons for transplantation. Here, we used an established neural induction protocol to differentiate two hiPSC lines (iPS1 and iPS2) and one human embryonic stem cell line (hESC; H9) toward a neurosensory lineage in vitro . Immunocytochemistry and qRT-PCR were used to analyze the expression of key markers involved in AN development at defined time points of differentiation. The hiPSC- and hESC-derived neurosensory progenitors expressed the dorsal hindbrain marker (PAX7), otic placodal marker (PAX2), proneurosensory marker (SOX2), ganglion neuronal markers (NEUROD1, BRN3A, ISLET1, ?III-tubulin, Neurofilament kDa 160), and sensory AN markers (GATA3 and VGLUT1) over the time course examined. The hiPSC- and hESC-derived neurosensory progenitors had the highest expression levels of the sensory neural markers at 35 days in vitro. Furthermore, the neurons generated from this assay were found to be electrically active. While all cell lines analyzed produced functional neurosensory-like progenitors, variabilities in the levels of marker expression were observed between hiPSC lines and within samples of the same cell line, when compared with the hESC controls. Overall, these findings indicate that this neural assay was capable of differentiating hiPSCs toward a neurosensory lineage but emphasize the need for improving the consistency in the differentiation of hiPSCs into the required lineages.
机译：新兴的感觉神经性听力损失疗法包括使用干细胞替代受损的听觉神经元（AN）。最终，重要的是这些替代细胞应与患者匹配以避免免疫排斥。由于可以直接从患者那里获得人诱导的多能干细胞（hiPSC），因此它们提供了产生与患者匹配的神经元进行移植的机会。在这里，我们使用已建立的神经诱导方案将两种hiPSC系（iPS1和iPS2）和一种人胚胎干细胞系（hESC; H9）朝着神经感觉谱系分化。免疫细胞化学和qRT-PCR用于分析在确定的分化时间点参与AN发育的关键标志物的表达。源自hiPSC和hESC的神经感觉祖细胞表达了后脑背标记（PAX7），耳廓耳廓标记（PAX2），神经前感觉标记（SOX2），神经节神经元标记（NEUROD1，BRN3A，ISLET1，？III-微管蛋白，神经丝kDa 160）。 ，以及在整个检查过程中的感官AN标记（GATA3和VGLUT1）。源自hiPSC和hESC的神经感觉祖细胞在体外35天时具有最高的感觉神经标志物表达水平。此外，发现从该测定法产生的神经元具有电活性。尽管分析的所有细胞系均产生功能性神经感觉样祖细胞，但与hESC对照相比，在hiPSC细胞系之间和同一细胞系样品中观察到标志物表达水平的差异。总体而言，这些发现表明该神经测定能够将hiPSC区分为神经感觉谱系，但强调需要提高hiPSC分化为所需谱系的一致性。

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