Deafness-in-a-dish: modeling hereditary deafness with inner ear organoids.
Deafness-in-a-dish: modeling hereditary deafness with inner ear organoids.
复制标题
培养皿中的耳聋：用内耳类器官模拟遗传性耳聋。
DOI：
10.1007/s00439-021-02325-9
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发表时间：
2022-04
期刊：
影响因子：
5.3
通讯作者：
Nelson, Rick F.
中科院分区：
文献类型：
--
作者：
Romano, Daniel R.;Hashino, Eri;Nelson, Rick F.
感音神经性听力损失（SNHL）是发达国家和发展中国家功能性残疾的主要原因。虽然助听器和人工耳蜗为许多SNHL患者提供了显着的益处，但两者都没有针对最终导致SNHL的细胞和分子功能障碍。更有针对性的方法，如生长因子，干细胞和基因疗法的成功开发，将需要对人类听力和耳聋的潜在分子机制有更深入的了解。不幸的是，人类内耳无法在不对听力或平衡器官造成重大不可逆损伤的情况下进行活检。因此，我们目前对人类耳聋的细胞和分子生物学的理解，以及更广泛的人类听觉系统，都是从动物模型的观察和实验研究中推断出来的，每一种都有自己的优势和局限性。2013年，研究人员描述了一种从多能干细胞（PSC）生成内耳类器官的方案，该方案可以作为动物模型的可扩展，高保真替代品。在这里，我们讨论了人类听觉系统的传统模型的优点和局限性，描述了PSC衍生的内耳类器官的产生和特征，并讨论了几种策略和最近的尝试，在体外模拟遗传性耳聋。最后，我们建议并讨论了进一步深入表征内耳类器官的几个重点领域，并讨论了这些人类内耳新型模型的转化应用。
Sensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide significant benefit to many with SNHL, neither targets the cellular and molecular dysfunction that ultimately underlies SNHL. The successful development of more targeted approaches, such as growth factor, stem cell, and gene therapies, will require a yet deeper understanding of the underlying molecular mechanisms of human hearing and deafness. Unfortunately, the human inner ear cannot be biopsied without causing significant, irreversible damage to the hearing or balance organ. Thus, much of our current understanding of the cellular and molecular biology of human deafness, and of the human auditory system more broadly, has been inferred from observational and experimental studies in animal models, each of which has its own advantages and limitations. In 2013, researchers described a protocol for the generation of inner ear organoids from pluripotent stem cells (PSCs), which could serve as scalable, high-fidelity alternatives to animal models. Here, we discuss the advantages and limitations of conventional models of the human auditory system, describe the generation and characteristics of PSC-derived inner ear organoids, and discuss several strategies and recent attempts to model hereditary deafness in vitro. Finally, we suggest and discuss several focus areas for the further, intensive characterization of inner ear organoids and discuss the translational applications of these novel models of the human inner ear.
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影响因子：
--
作者：
Bedford, H;de Louvois, J;Harvey, D
通讯作者：
Harvey, D
影响因子：
64.8
作者：
Chen, Wei;Jongkamonwiwat, Nopporn;Abbas, Leila;Eshtan, Sarah Jacob;Johnson, Stuart L.;Kuhn, Stephanie;Milo, Marta;Thurlow, Johanna K.;Andrews, Peter W.;Marcotti, Walter;Moore, Harry D.;Rivolta, Marcelo N.
通讯作者：
Rivolta, Marcelo N.
影响因子：
9.8
作者：
Ahmed, ZM;Riazuddin, S;Wilcox, ER
通讯作者：
Wilcox, ER
影响因子：
4.2
作者：
Cai R;Montgomery SC;Graves KA;Caspary DM;Cox BC
通讯作者：
Cox BC
DOI：
10.1002/cm.21227
发表时间：
2015-06
期刊：
Cytoskeleton (Hoboken, N.J.)
影响因子：
--
作者：
Andrade LR
通讯作者：
Andrade LR