An in vitro model of murine middle ear epithelium.

An in vitro model of murine middle ear epithelium.
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DOI:
10.1242/dmm.026658
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发表时间:
2016-11-01
影响因子:
4.3
通讯作者:
Bingle CD
Bingle CD
中科院分区:
医学2区
文献类型:
--
作者:
Mulay A;Akram KM;Williams D;Armes H;Russell C;Hood D;Armstrong S;Stewart JP;Brown SD;Bingle L;Bingle CD

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中耳炎 (OM) 或中耳炎症是最常见的儿科疾病,发病率很高。尽管复杂的病理生理学阻碍了对潜在疾病机制的理解,但很明显上皮异常是该疾病的基础。目前缺乏特征良好的中耳(ME)上皮体外模型来复制中耳复杂的细胞组成。在这里,我们报告了一种新型小鼠中耳上皮细胞(mMEC)体外气液界面(ALI)模型的开发,该模型概括了天然小鼠ME上皮的特征。我们证明 mMEC 可以分化为天然中耳内可见的各种细胞群。蛋白质组学分析证实,培养物从其顶端表面分泌大量先天防御蛋白。我们发现,mMEC 支持耳病原体不可分型流感嗜血杆菌 (NTHi) 的生长,这表明该模型可以成功地用于研究中耳中宿主与病原体的相互作用。总的来说,我们的 mMEC 培养系统可以帮助更好地了解中耳的细胞生物学,并提高我们对 OM 病理生理学的理解。该模型还有潜力作为验证治疗的平台,这些治疗旨在逆转支持 OM 发展的上皮重塑方面。摘要:小鼠中耳上皮体外耳病感染模型的开发和系统表征,作为更好地了解中耳炎复杂病理生理学的工具。
Otitis media (OM), or middle ear inflammation, is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. There is currently a lack of a well-characterised in vitro model of the middle ear (ME) epithelium that replicates the complex cellular composition of the middle ear. Here, we report the development of a novel in vitro model of mouse middle ear epithelial cells (mMECs) at an air–liquid interface (ALI) that recapitulates the characteristics of the native murine ME epithelium. We demonstrate that mMECs undergo differentiation into the varied cell populations seen within the native middle ear. Proteomic analysis confirmed that the cultures secrete a multitude of innate defence proteins from their apical surface. We showed that the mMECs supported the growth of the otopathogen, nontypeable Haemophilus influenzae (NTHi), suggesting that the model can be successfully utilised to study host–pathogen interactions in the middle ear. Overall, our mMEC culture system can help to better understand the cell biology of the middle ear and improve our understanding of the pathophysiology of OM. The model also has the potential to serve as a platform for validation of treatments designed to reverse aspects of epithelial remodelling that underpin OM development. Summary: Development and systematic characterisation of an in vitro otopathogenic infection model of the murine middle ear epithelium as a tool to better understand the complex pathophysiology of Otitis media.
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