Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1 Sec. 1 Jen-Ai Road, Taipei 100, Taiwan.
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1 Sec. 1 Jen-Ai Road, Taipei 100, Taiwan.
Acta Biomater. 2018 Mar 1;68:204-213. doi: 10.1016/j.actbio.2017.12.029. Epub 2017 Dec 26.
Olfactory dysfunction significantly influences patients' life quality, but currently has no adequate treatment. Poly (ethylene-co-vinyl alcohol) (EVAL) mediates cell adhesion, growth and modulates differentiation of neural stem cells. However, whether EVAL is a suitable substrate to establish an in vitro culture system that can promote development and differentiation of human olfactory neuroepithelial cells (HONCs) remains unexplored. This study isolates and cultures HONCs on controls and EVAL films for 21 days. The effects of treatment are assessed using immunocytochemistry, microarray analysis, quantitative PCR, ELISA and western blots following culturing. Most of the cell morphology on controls is epithelial and expresses markers of sustentacular cells (SCs), cadherin-1 and cytokeratin18, whereas the main population on EVAL presents as morphology with extended thin processes and possesses markers of mature olfactory sensory neurons (OSNs), olfactory marker protein (OMP). Microarray analyses reveal neuropeptide Y (NPY) and amphiregulin (AREG) are the two important regulating factors on EVAL films. HONCs cultured on EVAL films enhance the development of mature OSNs through NPY signaling, and significantly decrease the growth of SCs by blocking epidermal growth factor receptor (EGFR) activation. EVAL is a potential biomaterial to serve as an ideal substrate for treating olfactory dysfunction in the future.
Olfaction not only contributes to enjoyments of food, but provides a clue to escape from dangerous environmental hazards. However, loss of smell is commonly progressive and there is no good prognostic approach for olfactory dysfunction. Here, we use poly (ethylene-co-vinyl alcohol) (EVAL) to establish an in vitro culture system that promotes development and differentiation of human olfactory neuroepithelial cells. We show that EVAL not only enhances the development of mature olfactory sensory neurons through neuronpeptide Y signaling, but significantly protects the olfactory neuroepithelium from metaplasia by inhibiting EGFR activation. Therefore, EVAL is a potential biomaterial to serve as an ideal substrate for treating olfactory dysfunction in the future.
嗅觉功能障碍显著影响患者的生活质量，但目前尚无有效治疗方法。聚乙烯醇共聚物（EVAL）介导细胞黏附、生长，并调节神经干细胞的分化。然而，EVAL 是否适合建立体外培养系统，促进人嗅神经上皮细胞（HONC）的发育和分化，仍有待研究。本研究分离并培养 HONC 于对照和 EVAL 膜上 21 天。通过免疫细胞化学、微阵列分析、定量 PCR、ELISA 和 Western blot 检测培养后的细胞。对照组的大部分细胞形态呈上皮样，表达支持细胞（SCs）标志物钙黏蛋白 1 和角蛋白 18，而 EVAL 上的主要细胞形态呈延伸的薄突起，表达成熟嗅感觉神经元（OSN）标志物嗅觉标记蛋白（OMP）。微阵列分析显示神经肽 Y（NPY）和 Amphiregulin（AREG）是 EVAL 膜上的两个重要调节因子。HONC 在 EVAL 膜上培养时，通过 NPY 信号增强成熟 OSN 的发育，并通过阻断表皮生长因子受体（EGFR）激活显著减少 SCs 的生长。EVAL 是一种有前途的生物材料，可作为未来治疗嗅觉功能障碍的理想基质。
嗅觉不仅有助于享受食物，还为逃离危险的环境危害提供线索。然而，嗅觉丧失通常是进行性的，对于嗅觉功能障碍尚无良好的预后方法。在这里，我们使用聚乙烯醇共聚物（EVAL）建立了一个体外培养系统，促进人嗅神经上皮细胞的发育和分化。我们发现，EVAL 不仅通过神经肽 Y 信号增强成熟嗅感觉神经元的发育，而且通过抑制 EGFR 激活显著保护嗅神经上皮免受化生。因此，EVAL 是一种有前途的生物材料，可作为未来治疗嗅觉功能障碍的理想基质。
