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慢性鼻-鼻窦炎鼻息肉的神经分化能力。

Neuronal Differentiation Capability of Nasal Polyps of Chronic Rhinosinusitis.

机构信息

Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.

Fraunhofer Research Institution for Marine Biotechnology, EMB, Lübeck, Germany.

出版信息

Arch Immunol Ther Exp (Warsz). 2017 Oct;65(5):431-443. doi: 10.1007/s00005-017-0456-8. Epub 2017 Mar 9.

Abstract

Chronic rhinosinusitis with nasal polyps is considered a subgroup of chronic rhinosinusitis and a significant health problem, but the pathogenesis remains unclear to date. Therefore, we investigated the stemness to determine the role of stem cells in nasal polyps, with additional analysis of the neuronal differentiation potential of nasal polyp cells. We determined gene and protein expression profiles of stem cells in nasal polyp tissues, using whole genome microarray, quantitative real-time PCR (qPCR), immunohistochemistry, and flow cytometry. To evaluate the neuronal differentiation potential of nasal polyp cells, we used an efficient xenogeneic co-culture model with unsliced adult rat brain biopsies, followed by qPCR, immunohistochemistry, and growth factor antibody arrays. During gene expression analysis and immunohistochemistry, we were able to detect different stem cell markers, like Oct-4, Sox2, Klf4, c-Myc, ABCG2, Nanog, CD133, and Nestin, which confirmed the existence of stem cell like cells within nasal polyps. In addition, co-culture experiments give evidence for a guided differentiation into the neuronal lineage by overexpression of Nestin, Neurofilament, and GM-CSF. Our study demonstrated the expression of stem cell-related markers in nasal polyps. Furthermore, we characterized, for the first time, the stemness and neuronal differentiation potential of nasal polyp cells. These results gave new insights into the pathogenesis of nasal polyps and its therapeutic effectiveness could represent a promising strategy in the future.

摘要

慢性鼻-鼻窦炎伴鼻息肉被认为是慢性鼻-鼻窦炎的亚组,是一个重大的健康问题,但迄今为止其发病机制仍不清楚。因此,我们研究了干性来确定干细胞在鼻息肉中的作用,并进一步分析鼻息肉细胞的神经元分化潜能。我们使用全基因组微阵列、定量实时 PCR(qPCR)、免疫组织化学和流式细胞术来确定鼻息肉组织中干细胞的基因和蛋白表达谱。为了评估鼻息肉细胞的神经元分化潜能,我们使用了一种有效的未切片成年大鼠脑活检异种共培养模型,然后进行 qPCR、免疫组织化学和生长因子抗体阵列分析。在基因表达分析和免疫组织化学中,我们能够检测到不同的干细胞标志物,如 Oct-4、Sox2、Klf4、c-Myc、ABCG2、Nanog、CD133 和 Nestin,这证实了鼻息肉中存在类似干细胞的细胞。此外,共培养实验通过过表达 Nestin、神经丝和 GM-CSF 为神经谱系的定向分化提供了证据。我们的研究表明鼻息肉中表达了与干细胞相关的标志物。此外,我们首次描述了鼻息肉细胞的干性和神经元分化潜能。这些结果为鼻息肉的发病机制提供了新的见解,其治疗效果可能代表未来有希望的策略。

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