Building inner ears: recent advances and future challenges for in vitro organoid systems.
Building inner ears: recent advances and future challenges for in vitro organoid systems.
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DOI：
10.1038/s41418-020-00678-8
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发表时间：
2021-01
影响因子：
12.4
通讯作者：
Koehler KR
中科院分区：
文献类型：
--
作者：
van der Valk WH;Steinhart MR;Zhang J;Koehler KR
虽然内耳疾病很常见，但我们干预和恢复其感觉功能的能力是有限的。内耳的体外模型，如类器官系统，可以帮助识别新的再生药物和基因疗法。在这里，我们提供了对体外内耳模型现状的看法，以及如何提高其在转化研究中的适用性的指导。我们强调从多能干细胞生成内耳细胞类型是一个特别有前途的研究重点。最近的几项令人兴奋的研究表明，如何模仿胚胎和胎儿发育的发育信号线索，将干细胞分化为包含耳祖细胞、毛细胞和神经元的“内耳类器官”。然而，当前的分化方案以及我们对胚胎和胎儿内耳发育的总体了解对内耳的感觉上皮有偏见。我们建议需要更全面的观点来更好地模拟内耳的体外模型。展望未来，应关注内耳神经胶质细胞和间充质细胞类型的更广泛多样性，以及它们在发育过程中如何在空间或时间上相互作用。随着对上皮细胞、神经胶质细胞和间充质细胞命运规范的控制得到改善，内耳类器官将能够真正重现神经感觉功能和功能障碍。最后，我们讨论了发育中的内耳的单细胞图谱和技术创新将如何成为推动未来临床前应用的内耳类器官平台的关键工具。
While inner ear disorders are common, our ability to intervene and recover their sensory function is limited. In vitro models of the inner ear, like the organoid system, could aid in identifying new regenerative drugs and gene therapies. Here, we provide a perspective on the status of in vitro inner ear models and guidance on how to improve their applicability in translational research. We highlight the generation of inner ear cell types from pluripotent stem cells as a particularly promising focus of research. Several exciting recent studies have shown how the developmental signaling cues of embryonic and fetal development can be mimicked to differentiate stem cells into “inner ear organoids” containing otic progenitor cells, hair cells, and neurons. However, current differentiation protocols and our knowledge of embryonic and fetal inner ear development in general, have a bias toward the sensory epithelia of the inner ear. We propose that a more holistic view is needed to better model the inner ear in vitro. Moving forward, attention should be made to the broader diversity of neuroglial and mesenchymal cell types of the inner ear, and how they interact in space or time during development. With improved control of epithelial, neuroglial, and mesenchymal cell fate specification, inner ear organoids would have the ability to truly recapitulate neurosensory function and dysfunction. We conclude by discussing how single-cell atlases of the developing inner ear and technical innovations will be critical tools to advance inner ear organoid platforms for future pre-clinical applications.
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