Human middle ear cell lines as tools for the Otitis Media research community

人类中耳细胞系作为中耳炎研究界的工具

基本信息

批准号：
9316199
负责人：
Nikki Johnston
金额：
$ 23.1万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9316199
关键词：
Adult Affect African American Age Antimicrobial Resistance Archives Biopsy Specimen Brain Abscess Cell Culture System Cell Culture Techniques Cell Line Cells Cellular biology Characteristics Child Childhood Cholesteatoma Clinical Clinical Data Cochlear Implants Cohort Studies Communities Comparative Study Cytokeratin DNA Data Set Development Developmental Delay Disorders Diagnosis Disease Electron Microscopy Epithelial Cells Event Facial paralysis Female Functional disorder Future Genetic study Genotype Health Health Expenditures Healthcare Histopathology Human Human Cell Line Human Papillomavirus Immunohistochemistry In Vitro Inflammatory Inflammatory Response Interleukin-1 beta Investigation Language Lead Left Literature MUC5B gene Measures Meningitis Messenger RNA Methods MicroRNAs Molecular Molecular Biology Molecular Profiling Morbidity - disease rate Morphology Mucous body substance Natural Immunity Normal tissue morphology Operative Surgical Procedures Otitis Media Otitis Media with Effusion Pain Pathogenesis Pathway interactions Patients Phase Phenotype Physicians Physiology Positioning Attribute Prevalence Primary Cell Cultures Process Proteins RNA Race Recombinants Recording of previous events Recurrence Research Research Personnel Sampling Sex Characteristics Speech Speech Delay Subfamily lentivirinae System TNF gene Therapeutic Tissues Transfection United States Visit animal data antimicrobial base caucasian American cell immortalization comparative cost cytokine effusion established cell line experience experimental study hearing impairment high risk immortalized cell in vivo male middle ear novel pediatric patients peripheral blood racial difference sex tissue culture tool

项目摘要

Project Summary Otitis media (OM) affects more than 90% of children by the age of five and is the most common indication for antimicrobial therapy in children. OM is also the most common cause of hearing loss in children and can lead to significant educational and speech delays if left untreated. Surgical interventions for OM can cause significant morbidity including pain, facial paralysis, meningitis, and brain abscess formation. With an annual cost of $5 billion, OM has a large impact on health care nation-wide. Although the impact of OM is significant, the cellular and molecular events that regulate this disease process are still poorly understood. Investigations have been limited by having only a singular tool to conduct in vitro cell culture experiments. The objective of this R21 study is to develop, characterize, and compare immortalized middle ear (ME) epithelial cell lines derived from normal tissue obtained from both adult and pediatric cochlear implant patients without a history of OM and from patients with recurrent OM (ROM) and OM with effusion (OME). These cell lines will then be made available to the OM research community for further comparative analyses. Recent in vitro cell line, in vivo animal, and clinical data from a cohort study of OM patients and control CI subjects strongly support a key role for MUC5B and miRNA-146 in the pathophysiology of OM. The effect of recombinant TNF-α and IL-1β on MUC5B and miRNA146 expression levels, as they relate to the pathogenesis of OM, will be measured in these novel cell lines. These new tools will enhance, and potentially even change, assumptions which have been based on a narrow window of investigation. The cell lines established by this project will aid the OM research community to understand the differences between adult and pediatric patients and uncover potential mechanisms differentiating patients who suffer from OM from those who do not.

项目概要中耳炎 (OM) 影响 90% 以上的五岁儿童，是最常见的适应症儿童的抗菌治疗也是儿童听力损失的最常见原因，并可能导致儿童听力损失。如果不及时治疗，OM 的手术干预可能会导致严重的教育和言语延迟。每年都有明显的发病率，包括疼痛、面瘫、脑膜炎和脑脓肿。 OM 耗资 50 亿美元，对全国医疗保健产生了巨大影响。尽管 OM 的影响很大，但调节该疾病过程的细胞和分子事件由于只有一种体外进行的工具，人们对这些研究仍然知之甚少。该 R21 研究的目的是开发、表征和比较。永生化中耳 (ME) 上皮细胞系，源自成人和中耳正常组织无 OM 病史的儿科人工耳蜗患者以及患有复发性 OM (ROM) 和 OM 的患者这些细胞系将提供给 OM 研究界进行进一步研究。比较分析。来自 OM 患者和对照 CI 队列研究的最新体外细胞系、体内动物和临床数据受试者强烈支持 MUC5B 和 miRNA-146 在 OM 病理生理学中的关键作用。重组 TNF-α 和 IL-1β 对 MUC5B 和 miRNA146 表达水平的影响，因为它们与发病机制相关 OM，将在这些新型细胞系中进行测量。这些新工具将增强，甚至可能改变基于狭隘观点的假设。该项目建立的细胞系将帮助 OM 研究界了解成人和儿童患者之间的差异并揭示潜在机制区分患有 OM 的患者和未患有 OM 的患者。