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毛细胞再生:解读所有纷扰

Regeneration of Hair Cells: Making Sense of All the Noise.

作者信息

Kopecky Benjamin, Fritzsch Bernd

机构信息

Department of Biology, University of Iowa, Iowa City, IA, 52242, USA.

出版信息

Pharmaceuticals (Basel). 2011 Jun 1;4(6):848-879. doi: 10.3390/ph4060848.

Abstract

Hearing loss affects hundreds of millions of people worldwide by dampening or cutting off their auditory connection to the world. Current treatments for sensorineural hearing loss (SNHL) with cochlear implants are not perfect, leaving regenerative medicine as the logical avenue to a perfect cure. Multiple routes to regeneration of damaged hair cells have been proposed and are actively pursued. Each route not only requires a keen understanding of the molecular basis of ear development but also faces the practical limitations of stem cell regulation in the delicate inner ear where topology of cell distribution is essential. Improvements in our molecular understanding of the minimal essential genes necessary for hair cell formation and recent advances in stem cell manipulation, such as seen with inducible pluripotent stem cells (iPSCs) and epidermal neural crest stem cells (EPI-NCSCs), have opened new possibilities to advance research in translational stem cell therapies for individuals with hearing loss. Despite this, more detailed network maps of gene expression are needed, including an appreciation for the roles of microRNAs (miRs), key regulators of transcriptional gene networks. To harness the true potential of stem cells for hair cell regeneration, basic science and clinical medicine must work together to expedite the transition from bench to bedside by elucidating the full mechanisms of inner ear hair cell development, including a focus on the role of miRs, and adapting this knowledge safely and efficiently to stem cell technologies.

摘要

听力损失通过削弱或切断人们与外界的听觉联系,影响着全球数亿人。目前使用人工耳蜗治疗感音神经性听力损失(SNHL)的方法并不完美,这使得再生医学成为实现完美治愈的合理途径。人们已经提出并积极探索了多种受损毛细胞再生的途径。每条途径不仅需要深入了解耳朵发育的分子基础,还面临着在内耳这种细胞分布拓扑结构至关重要的精细环境中进行干细胞调控的实际限制。我们对毛细胞形成所必需的最小基本基因的分子理解有所进步,以及干细胞操作方面的最新进展,如诱导多能干细胞(iPSC)和表皮神经嵴干细胞(EPI-NCSC)的应用,为推进针对听力损失个体的转化干细胞疗法研究开辟了新的可能性。尽管如此,仍需要更详细的基因表达网络图谱,包括对微小RNA(miR)作用的认识,miR是转录基因网络的关键调节因子。为了充分发挥干细胞在毛细胞再生方面的真正潜力,基础科学和临床医学必须共同努力,通过阐明内耳毛细胞发育的完整机制,包括关注miR的作用,并将这些知识安全有效地应用于干细胞技术,来加快从实验室到临床的转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c95/4055959/6aee5d4cb91e/pharmaceuticals-04-00848f1.jpg

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